Open access peer-reviewed chapter

Valuable Food Molecules with Potential Benefits for Human Health

Written By

Liana Claudia Salanță, Alina Uifălean, Cristina-Adela Iuga, Maria Tofană, Janna Cropotova, Oana Lelia Pop, Carmen Rodica Pop, Mihaela Ancuța Rotar, Mirandeli Bautista-Ávila and Claudia Velázquez González

Submitted: September 12th, 2019 Reviewed: January 16th, 2020 Published: February 18th, 2020

DOI: 10.5772/intechopen.91218

Chapter metrics overview

1,184 Chapter Downloads

View Full Metrics

Abstract

The rapid development in the food supply chain has led to increased interest for quality in the food sector. In the last two decades, the human health and food safety have become essential. Health problems are highly related to diet and nutritional habits. The connection between nutrition and the development of various health problems is even more noticeable when close attention is given to every age group. Regarding the chemical composition of foods, a large number of bioactive compounds present in plants, fruits, vegetables, dairy products, meat, and fish are currently known. Bioactive compounds from food play an important role in prevention of illnesses. Covering essential aspects of health benefits of foods, the present chapter underlies without being exhaustive, the potential of valuable compounds such as soy isoflavones, phytochemicals, polysaccharides, probiotics, prebiotics, lipids, and marine proteins to be used as an effective prevention strategy for developing various human cancers, cardiovascular diseases, diabetes, and metabolic disorders.

Keywords

  • bioactive compounds
  • functional food
  • probiotics and prebiotics
  • phytochemicals
  • soy isoflavones
  • polysaccharides
  • seafood products

1. Introduction

The modifications occurred during globalization and the fast development of food production had led to new expectations from consumers regarding food and healthy diets [1]. Nowadays, as life expectancy has substantially extended, there is an acute demand for special foods that fulfill all the nutritional needs and help us maintain a balanced diet—a key role in sustaining human health [2]. Therefore, the food sector companies need to keep up with the consumers’ interests and needs while designing novel products. Moreover, health authorities, food engineers, scientists, health insurers, and customers seem to highlight an increased interest in illnesses prevention.

Today, food market is richer than ever, but the demand and the challenges seem to increase even more. Due to the globalization of the food market, an increasing number of special diets such as vegetarian or vegan, various food allergies, and intolerances have gained attention. Thus, scientists, food engineers, and health authorities seem to look for foods that bring added value and may even prevent diseases. These desiderates have brought the concept of “functional food” [3]. Thus, the consumers can correlate this category of foods with recognized health benefits [4].

Functional foods are known as healthy foods, medicinal foods, regulatory foods, fortified foods, nutraceuticals, and pharmacological foods [5]. A main statement or a clear definition of functional foods does not exist since all foods (conventional foods) provide energy and nutritional functions. Beyond these, functional foods contain elements that have the potential to sustain human health or reduce the risk for certain diseases [6, 7].

According to the potential medical benefits and properties of their ingredients, functional foods can be classified in several groups: dietary fiber, sugar alcohols, amino acids, oligosaccharides, glycosides, peptides and proteins, vitamins, cholines, lactic acid bacteria, minerals, polyunsaturated fatty acids, and others (e.g., phytochemicals and antioxidants) [8].

Studies have shown that an individual health status is influenced by diet even from very early stages. Special attention should be given so consumers have a well-balanced diet in order to avoid undernutrition and functional decline. In this light, specific recommendations are comprised in a 2014 report of Joint Research Centre, the European Commission’s in-house science service. The report summarizes the evidence on key micronutrient supplementations for preventing age-related diseases and draws attention on nutrition as a crucial element in healthy aging [9].

1.1 Consumer behavior: general overview

The quality of food is perceived by the consumers depending on intrinsic factors (freshness, organoleptic properties, health and hygiene safety) and external factors (origin, traceability, geographical indications and certification, labeling, health claims, production processes, etc.) [10].

In some countries, legislation policies have scrutinized the health claims labeling, as it represents a strategy that positively influences the purchase decision [11]. The European Union introduced important quality (origin) labels, in order to help consumers, namely Protected Designation of Origin (PDO) or Protected Geographical Identification (PGI) and Traditional Specialty Guaranteed (TSG). Moreover, the products’ quality and safety are regulated by the ISO 9001 (International Organization for Standardization) standards, which define the requirements of a quality system in order to ensure control throughout the production process and to prevent or detect any non-conformities. As an operational tool, the Hazard Analysis Critical Control Points (HACCP) system has been implemented, whose purpose is to achieve self-checking objectives [12].

Broadly, functional food refers to any food or food ingredient that may provide a health benefit beyond the nutritional ones. The market of functional foods covers foods that contain bioactive molecules such as polyunsaturated fatty acids [13], plants’ primary or secondary metabolites (polyphenols, anticipants, carotenoids, phytosterols [14, 15, 16, 17, 18, 19, 20], probiotics and/or prebiotics [21, 22] and others ( Figure 1 )).

Figure 1.

The bioactive molecules which add a supplemental value to regular food and provide functional benefits to human health.

The consumers’ perception regarding functional food is highly influenced by various factors such as food attributes (e.g., taste and flavor), the consumption behavior, the consumer’s knowledge, the potential benefits, purposes, diet preferences or restrictions, the consumer’s health problems, advertising, the label information, the packaging or the appearance, the brand and, not least, the product’s price [23, 24, 25, 26]. On the other hand, the food quality and safety play an important role in building the image of a product [27]. At the same time, attributes such as food palatability and healthiness are key elements in the consumer choices [28]. A recent research of Haasova and Florac has shown that manufactures need to focus on increasing the consumers’ orientation toward health goals and on reducing the consumers’ beliefs that healthy food equals tasteless food [29]. In another study, conducted in 2019 in the U.S., focused on consumers’ perceptions on natural and healthy foods, it was shown that consumers buy food products according to the several factors such as taste, price, healthiness, safety, and naturalness. Also, young consumers valued the food naturalness more compared to older consumers [30].

In most cases, functional foods have attractive forms and are certainly not commercialized as tablets or capsules [31]. Food producers constantly analyze the consumers’ behavior in relation to engineered foods, projected to maintain their health and prevent illnesses. The consumer’s keen interest in consuming natural products has challenged food industry to create innovative food products, developed for functional applications, but to keep the product as natural as possible. Due to their special indications, these products are consumed for a limited period of time. Thus, the main objective is to obtain functional foods using natural compounds and with minimal processing. A 2013 report [32] has estimated that sales of these special products will double by 2020. Similar to any food products, the market life and attractiveness of functional foods are following a Gaussian curve. Scientists report [33, 34] that a large number of functional foods get recalled soon after they enter the market, in most cases due to the reliance on technology, coupled with the absence of a thorough market research [35]. In order to explain what triggers the market failure of functional foods, it is mandatory to understand the consumer’s desire for products considered healthy.

In our opinion, the consumer’s attitude toward the potential benefits of these products for disease prevention and health improvement is the rhyme factor which dictates the consumption behavior. Thus, the consumer’s perception on the beneficial health effect of functional foods can essentially affect the purchasing process. These perceptions are, in turn, influenced by various factors such as involvement degree, lifestyle [36], food product characteristics (i.e., sensorial, nutritional, price, etc.) [37], package information, and package design [38]. In any case, the consumers’ trust in the functional claims is decisive in the purchase decision [39]. Information about food products and healthy diets is known and available to customers, and they evaluate all this information. Therefore, understanding the customer’s reasoning in evaluating the healthfulness of a functional product represents an important step in the process of designing functional foods. The big challenge is making the health benefits as credible as possible [40].

However, health claims are not the only factors that convince a customer to purchase functional foods. Other important factors are the product design, the cultural influences, the food matrix used as carrier for the active molecules, and the price. Among all the elements that influence the customer’s decision to buy functional foods, the confidence of obtaining well-being effects weighs the most. The customer’s certainty must represent the cornerstone for food products developers, stakeholders, and marketers.

1.2 Diet and health problems

Unhealthy diet is associated with regular consumption of foods and beverages rich in saturated fat, transfats, and polyunsaturated fats [41].

Worldwide, obesity is one of the major public health issues with multiple consequences: chronic diseases, including type 2 diabetes, coronary heart disease, and several cancers [42]. Besides the main factors that influence obesity, such as genetics, lack of physical activity, social and psychological factors, diet remains one of the major determinants that influences body weight. In the last 50 years, the prevalence of obesity has dramatically increased, reaching pandemic proportions, with more than 1 billion adults being overweight, of which at least 300 million are clinically obese. As a result, the consumption of functional foods has gradually expanded and gains more and more interest [43, 44].

In a recent study on health impact of dietary risks in 195 countries, authors have concluded that dietary habits are correlated with coronary heart sickness and other chronic non-communicable diseases, and urgent strategies to ameliorate the diet quality are required [45].

The diseases that prevail most in developed countries, the so-called “diseases of civilization,” are affecting the life quality of 100 times more people than mortal accidents [46]. In preventing overweight, obesity, or any chronic diseases (cardiovascular illnesses, various cancers, depression, and type 2 diabetes), the customer’s food choice can have a great impact on all related industries (i.e., food, pharmacy, etc.) [2, 47]. A first change in the consumers’ behavior can start by limiting the excessive food quantities and adjustment to a controlled, moderate food amount.

The maternal nutrition both before and during pregnancy, as well as the child’s nutrition after birth, will critically impact her or his later development and future health status [48]. The most common child health problems caused by an unbalanced diet are iron deficiency anemia, vitamin D deficiency, obesity, dental caries, and faltering growth [49]. In toddlers, the prevalence of iron deficiency anemia and severe obesity is each approximately 2%. Later in life, iron deficiency has been associated with potential neurodevelopmental impairments, while obesity in childhood may continue into adulthood, accompanied with adverse cardiometabolic outcomes [50].

Malnutrition, in all its forms, includes undernutrition (including wasting, stunting and micronutrient deficiency/insufficiency) and overweight and obesity. Acknowledging the need of accelerated actions against malnutrition and the need to promote a healthier maternal, infant and child nutrition, WHO has elaborated, in 2012, a group of six general nutrition targets that by 2025 aim to: (1) attain a 40% reduction in the number of children under 5 who are stunted; (2) achieve a 50% reduction of anemia in women of reproductive age; (3) achieve a 30% reduction in low birth weight; (4) ensure that there is no increase in childhood overweight; (5) increase in the rate of exclusive breastfeeding in the first 6 months up to at least 50%; and (6) reduce and maintain childhood wasting to less than 5% [51]. Some of these targets have been extended to 2030.

In adults, half of the total chronic disease deaths are attributable to cardiovascular diseases. Accelerating trends can be seen also for obesity and diabetes as more patients are diagnosed at an early age. The list of most common chronic diseases in adults and elderly is completed by hypertension, hypercholesterolemia, arthritis, depression, Alzheimer’s disease, osteoporosis, and chronic obstructive pulmonary disease [52]. However, these chronic diseases are largely preventable and diet plays a key role in preventing or promoting chronic illnesses.

According to a standardized case-control study, eight of nine modifiable risk factors associated with acute myocardial infarction are influenced by diet. Most of these factors act by promoting atherogenesis, by modulating vasodilation, prothrombotic and pro-inflammatory processes that trigger the endothelial dysfunction, an early predictor of atherosclerosis [53, 54]. Apparently, vascular inflammation is associated with unhealthy dietary patterns, overweight and obesity, smoking habit, alcohol consumption and sedentarism [54].

In a population-based prospective cohort study, higher dietary intake of vitamin E, but not vitamin C, beta carotene, or flavonoids was modestly associated with lower long-term risk of dementia. Vitamin E antioxidant mechanisms are not fully understood, but it could improve cognitive performance by diminishing the effects of β-amyloid, as it was shown in experimental studies [55].

1.3 Health benefits of functional food

With the emergence of the term FOSHU (Foods for Specific Health Use), in the early 80s in Japan, the impact of food on health has gained much attention in the recent decades. However, the scientific community has not fully agreed on what is covered by the term “functional foods.” The FUFOSE (Functional Food Science in Europe), for its part, has defined them as follows: “A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, thus either improving, the general physical condition or/and decreasing the risk of the generation of disease” [56]. However, the study of food, focused on therapeutics, is not something new and if we go back to the past, the classification of the use of food and plants with therapeutic properties goes back to the Mid Paleolithic age [57]. Also, during the history of humankind, the health benefits of food have been capitalized in traditional medicines such as Unani, Traditional Chinese Medicine, and Ayurveda. In this same sense, Persian Medicine (PM) in the Islamic era (980 AD) already considered the classification of certain foods as potential drugs with a significant role in health, not only as mere energy providers, but also as being able to affect the human body by changing even the temperament and personality of individuals. Faced with a disease, PM first considered a special diet for the patient using specific foods, and if the patient’s health did not improve, drug therapy was the second option [58]. Already at that time, there was a classification for food and drugs very similar to the classification currently available for functional foods, nutraceuticals, and pharmaconutrients.

Foods are classified as functional after their effects have been demonstrated in well-designed and properly executed intervention studies in humans [8]. Functional food can play an essential role in disease treatment and prevention.

The beneficial health properties of various foods have been scientifically recognized thanks to the analytical development in identifying and characterizing their chemical composition and due to the clinical studies that have assessed their role in various pathologies. Studies based on in vitro and cell-culture systems, preclinical interventions using animals, and clinical trials have investigated the potential of functional foods to combat various human cancers, cardiovascular disease, diabetes, metabolic disorders, inflammation, high blood pressure, microbial, viral and parasitic infections, mental diseases, spasmodic disorders, ulcers, etc. [59].

The relationship between food and human health is extremely tight, and World Health Organization has stated that “A healthy diet helps to protect against malnutrition in all its forms, as well as noncommunicable diseases (NCDs), including such as diabetes, heart disease, stroke, and cancer. Unhealthy diet and lack of physical activity are leading global risks to health.” Regarding the chemical composition of foods, a large number of bioactive compounds present in plants, fruits, and vegetables are currently known, such as polyphenols or carotenoids and nowadays it is known that the concentration of these bioactive compounds is variable depending on the parts of the plant, season, climate, and the particular growth phase [60].

The Global Burden of Disease study has reported that unhealthy diets represent a risk factor for disease, morbidity, and disability both in Canada and worldwide [61]. Certain diets, such as vegetarian diet (rich in antioxidants), the Mediterranean diet (high in olive oil with monounsaturated fatty acids), and the Okinawan diet (high in fruits, vegetables, and omega-3 fatty acids in fish) can impede the development of age-related diseases. More specifically, Everitt et al. reported in their study that epidemiological research consistently demonstrates that the intake of certain foods is correlated with cardiovascular disease risk [62].

Daily diet can be improved by including essential fatty acids, minerals, vitamins, and proteins from fish and meats and increasing the intake of calories and proteins from nutritionally appropriate sources (nuts and seeds, pulses, soy products, dairy products) [63].

Advertisement

2. How probiotics and prebiotics sustain human health: a correlation with functional food intake

A worldwide known fact is that the gut microbiota composition has a strong influence on the host health and metabolism [64, 65]. More than 500 species of bacteria coexist in the human gastrointestinal tract (GI), and among them, about 95% of the total number of cells in the colon [66]. Many of the indigenous GI habitants are probiotic bacteria cells that pertain to the genera Lactobacillus, Bifidobacterium, or Enterococcus. Notably utilized and commercialized probiotics are belonging to the first two genera. An extremely studied topic for the past two decades was the gut microflora, being in the spotlight of food and medicine scientists, food engineers, authorities, and customers as well. In the functional food market, the pathway has two lanes, namely how functional foods influence gut microbiota and how common foods can incorporate these valuable cells and become functional foods with important characteristics ( Figure 2 ).

Figure 2.

Probiotic functional foods characteristics.

Even though the presence of probiotics in different functional food matrices has been widely studied, the amount of documented therapeutic applications and clinical trials is very modest. The influence of different functional foods on gut microbiota is now in the spotlight of many researchers. Most of the studies regarding the effect of functional foods on gut microbiota fail to prove the causative role. In most of the cases, the disease is treated with certain functional food and, afterward, the gut microbiota composition is tested and correlated, correct or not, with the cause of the disease alleviation. But, stating this may be as true as the affirmation “the consequences of diseases alleviation were the registered changes in the gut microbiota.” Today, the concept of functional food (i.e., foods containing dietary fibers, polyunsaturated fatty acids, polyphenols, etc.) utilization in order to obtain a certain response with respect to a disease is embraced by many customers, but the modulation of gut microbiota by changing eating patterns and/or diet composition is still a novel practice [67]. In the attempt to evaluate the changes in the gut microbiota composition in different diseases and after ingestion of functional foods, the literature reports two approaches for the in vivo tests on mice. The first one is the mice treatment with antibiotics to see whether disorder of the gut microflora could cut off the curative effects of functional foods on a certain illness. The limitations of this method arise from the fact that antibiotics could not entirely eradicate the effect of gut microbes on the evolution of the diseases, as they could not completely eliminate microbes from the gut. A different approach is the utilization of germ-free mice [68, 69]. Thus, it tests if a specific functional food product may be unsuccessful in the treatment of the targeted disease in germ-free mice. This fact reveals that the target of the ingested functional food may not be the gut microbiota. However, in these times when microbiota-targeted nutrition has become a frequently proposed technique, we predicted more studies that can establish a causal connection between functional foods ingredients, host health, and gut microbiota.

Another approach, in order to modulate the gut microflora, is to ingest functional foods, which have as active ingredient viable probiotic cells [70], prebiotics (the probiotic food) [71], and/or synbiotics (pro and prebiotics) [72]. Nowadays, probiotic cells are included in more and more products, extending the size of functional food market. Not long ago, probiotic cells were associated mostly with dairy and fermented foods, but things have been considerably changed. There are several studies that have demonstrated good viability cells in products such as chocolate [73, 74], bread [75], juices [76], jelly [77], meat [78, 79] and even edible films or coatings [80]. Results of these studies demonstrate, besides the good viability of the probiotics during processing, shelf life and even gastrointestinal passage, no negative changes regarding the food structure or sensorial properties [81]. However, reports regarding the concrete influence of functional foods probiotics on the consumer health are modest. Health benefits of probiotics intake are multiple and based on scientific evidence. Among the multiple well-being advantages related to probiotic consumption, we will discuss the most studied and known ones.

One of the health benefits of probiotic cell intake is its capacity to regulate the host’s intestinal microflora and the general well-being. An individual’s intestinal microflora composition is rather well balanced after early infancy, in healthy subjects, even though variations exist among subjects [82]. One of the most important actions of probiotics is to positively influence intestinal microbiota. Evidence shows that Lactobacilli intake ensures a reduction of pathogenic gram-negative anaerobes, such as Clostridia or Enterobacteriaceae [83]. Postsurgical period predisposes the individual to infections with gram-negative anaerobe bacteria or with sulfite-reducing Clostridia, leading to inflammatory response due to the secreted endotoxins. The mentioned pathogens are inhibited by Lactobacillus due to their capacity to produce antimicrobial metabolites (i.e., bacteriocins, hydrogen peroxide) and other valuable substances such as short-chain fatty acids. Beside Lactobacillus, Bifidobacterium intake may reduce the butyrate-producing anaerobes [84]. Another study [85] revealed the efficacy of Lactobacillus in Rotavirus infections. Probiotics proved to have a positive effect in reducing the duration of acute rotavirus diarrhea in children in comparison with control. Thus, we can conclude that the consumption of viable probiotic cells, trough functional foods or as supplements, can considerably improve the composition of intestinal microbiota, leading to health benefits that can confer a better life to the consumer.

Treatment or amelioration of diarrhea is a promising and extensively studied technique. Diarrhea causes may be multiple and need to be approached with different types of probiotic species, in single or multiple formulations. A review, published by Marteau et al., pointed out that these valuable cells have good results in treating diarrhea induced by antibiotic treatment, Rotavirus or/and Gastroenteritis, but they are less efficient for traveler’s diarrhea [86]. Another appreciated health benefit induced by probiotic ingestion is the amelioration of irritable bowel syndrome (IBS) symptoms. Even if the cause of this disorder is still unknown, the symptoms are very clear, namely abdominal pain, constipation or diarrhea, and infrequent nausea, fluid retention, tiredness, and bloating. For most of the patients suffering from IBS, an imbalance in the intestinal microbiota can be found. In most of the cases, a decreased number of bifidobacteria can be observed, with an increase in the facultative anaerobes pathogens [87]. Many of the mentioned intestinal disorders may lead, in time, to carcinomas.

Advertisement

3. Phytochemicals: general overview, potential applications, and health benefits

Fruits are a source of active compounds, such as vitamins (C and A), minerals (electrolytes), and more recently phytochemicals, especially with antioxidant properties, which include phenolic compounds, flavonoids, lignins, tocopherol (vitamin E), carotenoids, betaine, colin, saponins, and phthalates [88]. Because of their importance, we are going to focus on polyphenols.

Polyphenols are natural compounds characterized by the presence of phenol, catechol, and resorcinol (benzene rings with several hydroxyl groups in o, m, and p positions). In phenolic acids, the presence of a carbonyl group, such as aromatic acid, ester, or lactone, enhanced its antioxidant activity as well as when its carbonyl group is separated from the aromatic ring [89, 90]. Phenolic acids are derivatives of hydroxycinnamic acid such as p-hydroxybenzoic, 3,4-dihydroxybenzoic, vanillic, syringic, p-coumaric, caffeic, ferulic, sinapic, chlorogenic acid, and rosmarinic acid. The derivatives of cinnamic acid are more active antioxidants than the derivatives of benzoic acid derivatives [90, 91]. There are three structure groups responsible for the determination of free-radical scavenging and antioxidant activities of flavonoids: a catechol moiety of the B-ring, the 2,3-double bond in conjugation with a 4-oxo function of a carbonyl group in the C-ring, and presence of hydroxyl groups at the 3 and 5 positions [90]. They are classified as flavonols, flavons, flavanons, flavanols, flavandiols, isoflavonoids, cathechins, chalcones, dihydrochalcones, anthocyanidins, leucoanthocyanidins, proanthocyanidins, or condensate tannins [92].

Some drinks such as coffee, tea, beer, and wine; fruits such as apple, orange, guava, papaya, and grape; vegetables such as, zucchini, beet, avocado, watercress, chili, and tomato; dry fruits as nuts; and cacao are important sources of polyphenols and other antioxidants [93, 94, 95]. Polyphenols possess several pharmacological activities and are characterized by their antioxidant activity, which depends on the substitution in either ortho- or para-position, while the substitution in meta-position has a rather limited effect. It is known that the polyphenols consumption could be related with the decrement of chronic and degenerative diseases such as diabetes, cancer, cardiovascular, neurodegenerative, and antitumoral diseases, promoter of the immune system, anti-inflammatory, skin protective effect from UV radiation, antibacterial and antifungal activities [96, 97, 98, 99, 100].

Free radicals are generated as a result of normal cell metabolism. These reactive oxygen species (ROS) cause lipids, proteins, and nucleic acids damage in cells and modulate several signaling pathways [101]. As a consequence, different pathologies such as chronic and degenerative diseases can develop. All aerobic organisms have antioxidant defenses, including antioxidant enzymes and antioxidant constituents to remove or repair the damaged molecules. Also, the natural antioxidants from certain foods can be beneficially used to remove oxygen and reactive oxygen species [90, 102].

Polyphenols are involved in cell cycle regulation and may inhibit the progression of cancer in many organs or even block latent tumors due to their anti-angiogenic and anti-inflammatory properties. As for the origins and causes of various cancer types, they are not yet well established. However, it is known that high levels of free radicals such as reactive oxygen species (ROS) produce lipid peroxidation that induces various cell injuries. These injuries can later lead to cancer development [103]. In this context, polyphenols studies have shown that they can regulate cell proliferation and specific protein modulators associated with cell cycle [104]. Likewise, polyphenols can control cancer cell progression in many organs [105]. They also have the capacity to block latent tumors by direct inhibition of tumor cells or by anti-angiogenic and anti-inflammatory properties and protect deoxyribonucleic acid (DNA) from lesions caused by reactive oxygen species. Using these mechanisms, cancer progression can be hindered and pro-apoptotic mechanisms are then triggered [105].

Flavonoids possess antioxidant activity due to their structures, which is capable of donating an electron or chelate metal ions. Some foods such as blueberry, red wine, green tea, and cocoa have been studied for their antioxidant properties in order to prevent diseases [106]. The group of antioxidants includes mainly vitamins (ascorbic acid, tocopherol) and flavonoids such as quercetin, pycnogenol, and flavan-3-ol monomers and oligomers [100, 107, 108]. Flavonoids and other phenolic compounds showed cardiovascular protection by improving the endothelial function, reducing the oxidative stress, lowering arterial pressure, improving the elasticity of the internal blood vessels’ walls, or by inhibiting platelet agglutination. These properties could prevent blood clot formation in the arteries, and can positively influence blood lipid balance and insulin sensitivity [109, 110].

Specific components of fruits may also show protective effect in human organism. Quantitatively, the most important carotenoids in the human diet are β-carotene, lycopene, lutein, β-cryptoxanthin, zeaxanthin, and astaxanthin [111, 112]. Lycopene is a carotenoid found in brightly colored fruits and vegetables, and research suggests that foods containing carotenoids may protect against lung, mouth, and throat cancer [113, 114]. In addition, a study suggests that lycopene may help protect men against prostate cancer, especially in aggressive forms [115].

Finally, the consumption of fruits rich in polyphenols and carotenoids could reduce the incidence of developing chronic degenerative diseases, stroke, and cancer [106, 116, 117, 118]. Nowadays, the use of extracts and secondary metabolites of plants and foods in different pathologies is extremely well documented [105]. Table 1 presents some pharmacological activities of several secondary metabolites.

Cardioprotective activity
Kaempferol, rutin, luteolin, quercetin, resveratrol Activity against doxorubicin-induced cardiotoxicity [119]
Gallic, ellagic, syringic, ferulic, cinnamic acids, and quercetin Attenuate oxidative stress in H9c2 cardiomyoblasts [120]
Aspalathin and phenylpyruvic acid-2-O-β-D-glucoside Protect myocardial infarction caused by chronic hyperglycemia [121]
Puerarin Protects myocardium from ischemia and reperfusion damage (Ca2+-K+ channel and the protein kinase C activated) [122]
Naringenin-7-O-glucoside Activity against doxorubicin-induced cardiotoxicity, protects against cardiomyocyte apoptosis [123]
Isorhamnetin Effect against cardiotoxicity of doxorubicin [124]
Antibacterial activity
Gliricidin 7-O-hexoside and quercetin-7-O-rutinoside Proteus mirabilis, P. vulgaris, and Pseudomonas aeruginosa [125]
3,4,7-trihydroxyflavone Providencia stuartii and Escherichia coli [126]
Pseudarflavone A and 6-prenylpinocembrin E. coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus [127]
2-(3,4 dihydroxy-phenyl) 3,5,7-trihydroxy-chromen-4-one Pseudomonas aeruginosa [128]
Kaempferol P. acnes [129]
Strictinin Propionibacterium acnes and Staphylococcus epidermidis [130]
Anticancer activity
Flavopiridol Treatment of lymphomas and leukemia [131]
Quercetin Induces apoptosis of each one of these cell lines:
acute lymphoblastic leukemia MOLT-4 T-cells, human myeloma U266B1 cells, human lymphoid Raji cells
Prostate adenocarcinoma LNCaP cells, human prostate PC3 cells
Colon carcinoma CT-26 cells, Pheochromocytoma PC12 cells, Estrogen receptor-positive breast cancer MCF-7 cells, ovarian cancer CHO cells [132]
Induces microRNAs involved in Notch signaling/cell-fate determination of the tested pancreatic cancer (primary pancreatic cancer cell line ASANPaCa, AsPC1, and PANC1) [133]
Gliricidin7-O-hexoside and Quercetin 7-O-rutinoside Human hepatoma HepG2 and carcinoma HeLa cells [125]
Genistein Inhibits the activation of Nuclear factor kappa B (NF-kB) involved in balance of cell survival and apoptosis on prostate cancer [134]
Curcumin Acts as a pro-apoptotic agent in skin cancers [98]
Inhibits melanoma cell proliferation related to epigenetic integrator UHRF1 [135]
Inhibits the proliferation of human prostate cancer cell lines such as LNCaP and 22Rv1 cells [136]
Anti-inflammatory activity
Apigenin, C-rhamnosyl flavones, and luteolin Reduce nitric oxide levels in macrophages, inhibit the activity of phospholipase A2 [137]
Quercetin, apigenin, hesperidin, and luteolin Anti-inflammatory effects [138]
Astilbin Anti-inflammatory effects observed in vitro after lipopolysaccharide-induced inflammation suppresses nitric oxide production, tumor necrosis factor-α (TNF-α), mRNA expression of inducible nitric oxide synthase [139]
Acteoside Inhibits inflammation in LPS-induced lung injury in mice, inhibits inflammation in lung epithelial cells A549, inhibits NF-kB activation in LPS-induced mice and lung epithelial cells A549 [140]
Skin protective effect from UV radiation
Apigenin Skin protective effect of damage caused by UV light [141]
Quercetin Inhibits UVB-induced skin damage in hairless mice [142]
Silybin Prevention of apoptosis in UVB-exposed human epidermal keratinocytes [143]
Genistein Photoprotective activity in human skin against photocarcinogenesis by inhibiting UV-induced DNA damage [144]
Equol Prevents damage from UV-induced erythema-associated edema, inhibits DNA photodamage [145]
Metabolic syndrome
Genistein Improves factors of risk for diabetes and cardiovascular disease in postmenopausal women with MetS [146]
Acteoside Antihypertensive activity in lowering systolic blood pressure (SBP) and diastolic blood pressure (DBP) [147]

Table 1.

Pharmacological activities of secondary metabolites from food and plants.

Advertisement

4. Soy isoflavones: evidence-based health benefits and official recommendations

Isoflavones are polyphenolic plant metabolites produced almost exclusively by the members of the Fabaceae family. More specifically, isoflavones are part of the flavonoids group, which share the 2-phenylchromen-4-one backbone. Due to the structural similarity with 17-β-estradiol, the primary female sex hormone, isoflavones have been included in the wide family of phytoestrogens. The main sources of the natural isoflavones are soy beans, chickpeas, fava beans, pistachios, and peanuts. Of these, physiologically relevant amounts are found only in soybeans and soy-derived foods, and raw soybeans containing 1.2–4.2 mg/g dry weight isoflavones. Besides isoflavones, soy is also an excellent protein source and contains vitamins, minerals, and insoluble fibers. Genistein, daidzein, and glycitein ( Figure 3 ) are the biologically active aglycones from soy-based foods and red clover. Other isoflavones present in various plants are biochanin A and formononetin, which can be converted through 4′-O-demethylation to genistein and daidzein, respectively. Generally, the soy aglycones are conjugated with a glucose moiety through the -OH group from position C7 (7-O-glucoside) and form the β-glycosides, genistin, daidzin, and glycitin [148, 149].

Figure 3.

The chemical structures of soy isoflavones.

The aglycones are rapidly absorbed in the small intestine by spontaneous, passive diffusion. The free aglycone forms are only merely present, as soy beans and non-fermented soy foods mostly contain the glycosylated forms. These conjugates need to be prior converted to the bioactive aglycones. Their hydrolysis is completed by β-glucosidases from intestinal bacteria, or an enzyme in the intestinal mucosa. Daidzein and genistein aglycones can also derive from formononetin and biochanin A hydrolysis [150]. Soy isoflavones have drawn the attention of the scientific community due to their multiple medicinal and therapeutic proprieties. The health benefits provided by soy isoflavones are presented in Figure 4 [151]. These potential benefits will be presented herein.

Figure 4.

The health benefits of soy isoflavones.

4.1 Soy isoflavones and cancer

Perhaps the most controversial aspect related to soy isoflavones is linked to their potential role in chemoprevention. Most studies have investigated the correlation between soy consumption and breast or prostate cancer, but several studies have also investigated the role of soy isoflavones in other malignancies, such as: colon cancer, liver adenocarcinoma, bladder cancer, or brain tumor [151].

The perception that soy isoflavones possess anticancer proprieties derives from epidemiological data, which showed that Asian women who regularly consume soy or soy-based foods have a significant lower breast cancer risk than Caucasian women who do not consume soy as part of their daily diet [152]. These epidemiological studies have indicated an inverse correlation between polyphenol-rich dietary intake and cancer development.

The differences between the daily isoflavone intake in the US, Europe, and Asia are significant: non-Asian populations consume less than 3 mg isoflavones per day, whereas Japanese and Shanghai Chinese populations consume approximately 40 mg or more [153]. Moreover, the prostate cancer incidence in Asian immigrants moved to Western countries was found to be higher compared to the one from their countries of birth [154]. Also, when Asian women migrate to the West, their daughters born in the West have a higher risk for developing breast cancer compared to their mothers [152]. This growth can be attributed to dietary patterns and underlines, once more, the importance of nutritional factors in cancer development.

Concerns related to the potential proliferative effects of soy isoflavone on breast cancer cells have emerged with in vitro data, when the effects of isoflavones were tested on estrogen receptor positive breast cancer cell lines. According to several cell-based studies, isoflavones, and, especially genistein, exhibited a dose-dependent effect. When estrogen-dependent cells were exposed to relatively low concentrations of genistein (0.01–10 μM), the cell growth and proliferation were promoted, while higher concentrations of genistein (>20 μM) have displayed inhibitory effects. In contrast, in estrogen-independent breast cancer cells, this twofold effect was not observed. In these cells, isoflavones have induced only antiproliferative effects, particularly after high dose exposure [155, 156, 157, 158]. These observations have concluded that genistein can induce estrogenic and antiestrogenic effects (depending on the dose), but other cytotoxic mechanisms might be involved as well.

The dual effect of genistein observed in in vitro studies was confirmed using a postmenopausal animal model. In low-estrogen conditions, dietary genistein acted in a cumulative manner to stimulate cell growth, suggesting that consumption of genistein-rich products might not be completely safe for postmenopausal women diagnosed with estrogen-dependent breast cancer [159]. However, rodents have higher circulating concentrations of biologically active genistein compared to humans due to a different phase II metabolism of isoflavones. Thus, gaining insight into the effects of isoflavones, especially genistein, using a mouse model might cast doubt and conclusions might not be extrapolated to humans [160].

Behind the antiestrogenic effect, isoflavones can act through a plethora of cellular and molecular mechanisms to inhibit breast cancer cell growth. Genistein was shown to interfere in cell proliferation and survival by blocking important signaling pathways such as NF-ĸB pathway activation or PI3K/Akt/mTOR pathway. Moreover, genistein can trigger cell apoptosis, promote antioxidant defense and DNA repair, and inhibit the progress of tumor angiogenesis and metastasis. The aglycone can also interfere in other important ER-independent signal transduction pathways [157].

The non-cytotoxic effects of genistein and other isoflavones have been validated by the extensive clinical and epidemiologic data. Clinical trials consistently showed that isoflavone consumption does not adversely affect the markers of breast cancer risk. Furthermore, soy intake after breast cancer diagnosis significantly reduced the cancer recurrence and improved the overall survival [161].

A recent notification made by the American Cancer Society (ACS) reassures breast cancer survivors that soy foods are healthy and safe. Moreover, the health benefits of soy consumption appear to outweigh any potential risk and eating traditional soy foods such as tofu, tempeh, miso, and soymilk may even lower the risk of breast cancer, especially among Asian women. Beyond its isoflavone content, soy also represents an excellent protein source. However, patients are advised against taking soy supplements, which contain much higher isoflavone concentrations than food, until more research is done [162].

A similar position was adopted also by the American Institute for Cancer Research, which states that consumption of moderate amounts of soy foods does not increase a breast cancer survivor’s risk of recurrence or death. The institute also explains that a moderate amount of soy consumption is represented by 1–2 standard servings (one serving averages about 7 g of protein and 25 mg isoflavones) daily of whole soy foods (tofu, soy milk, edamame, and soy nuts). According to studies, up to 3 servings/day—up to 100 mg/day of isoflavones—consumed in Asian populations long-term does not link to increased breast cancer risk [163].

4.2 Soy isoflavones and cardiovascular diseases

Clinical trials have shown that soy isoflavones can attenuate blood pressure, but this effect is more probable to occur in hypertensive or equol-producing individuals [164]. Also, a daily average consumption of 30 g soy protein was associated with a significant improvement in lipoprotein risk factors for coronary heart disease [165]. Similar to soy proteins, soy isoflavones were also shown to improve cardiovascular disease risk markers. Apparently, supplementation of soy protein with isoflavones (15 g soy protein with 66 mg isoflavone) for 6 months significantly improved the cardiovascular markers in women during the early menopause compared to soy protein alone (15 g soy protein) [166].

The molecular mechanism explaining the cardiovascular effects of soy isoflavones are multiple. First, isoflavones can mimic estrogen action and interact with estrogen receptors inducing receptor conformations similar to the action of selective estrogen receptor modulators (SERMs). Moreover, isoflavones can promote the activation of endothelial nitric oxide synthase in blood vessels through signaling pathways such as ERK1/2, PI3-Kinase/Akt, and cAMP. Apart from vasculature, isoflavones can also have a renal mechanism, increasing renal blood flow and sodium excretion. Finally, soy isoflavones can have humoral mechanisms, interacting with the renin-angiotensin-aldosterone axis [167].

The cardioprotective effects of soy have been demonstrated in multiple clinical trials, which have finally led to the FDA approval of soy consumption in order to lower the cardiovascular risk. According to 101.82 FDA health claim “Soy protein and risk of coronary heart disease (CHD),” the daily dietary intake level of soy protein that has been associated with reduced risk of coronary heart disease is 25 grams or more per day of soy protein. Moreover, when soy protein is included in a low saturated fat and cholesterol diet, it helps lower blood total and LDL cholesterol levels [168].

In 2017, the FDA proposed to revoke the healthy claim released in 1999 for soy protein, citing mixed results in more recent studies of the heart benefits of soy. However, a recent cumulative meta-analysis of the data selected by the FDA indicates continued significance of total cholesterol and low-density lipoprotein cholesterol reduction after soy consumption [169].

4.3 Soy isoflavones in diabetes mellitus

There are multiple animal and cell-culture studies demonstrating that soy isoflavones, and particularly genistein, exert anti-diabetic effects at physiologically relevant concentrations (<10 μM) [170]. However, a clear conclusion over the anti-diabetic properties of soy isoflavones has not been drawn.

In humans, data on soy isoflavone intake are relatively limited. Still, most studies have linked soy consumption to positive outcomes on glycemic control and insulin resistance. A meta-analysis of observational studies suggested an inverse association between soy food consumption and risk of type 2 diabetes, especially in women and Asians [171]. This is in accordance with another study, which suggested that post-menopausal women who consumed a high soy diet had a lower fasting insulin, compared with those with no daily genistein consumption. Besides, women with high genistein intake had a significantly lower body mass index and waist circumference [172]. Recently, another study has drawn a similar conclusion, that dietary soy intake is inversely associated with risk of type 2 diabetes in Japanese women, but not in men [173].

As a molecular mechanism, most studies showed that genistein treatment increased β-cell proliferation in cell culture models and reduced apoptosis, protecting against β-cell mass destruction. The exact mechanisms appear to involve cAMP/PKA, NF-κB, and ERK-1/2 pathways signaling pathway and several studies suggested an effect on epigenetic regulation of gene expression. Furthermore, genistein has been shown to protect against oxidative stress and inflammation, and to enhance glucose homeostasis through stabilization of pancreatic β-cell function [170, 174].

Although many studies have investigated the benefit of soy isoflavone consumption of blood glucose, well-designed studies are needed to fully understand the underlying mechanisms and evaluate the exact effects of soy isoflavones on diabetes.

In April 2018, the American Diabetes Association (ADA) released a nutrition report with eating recommendations to help manage and prevent diabetes, and also to prevent complications such as heart disease. In this report, there are no amendments related to soy consumption for diabetic patients. The only specific remark is for patients with diabetic kidney disease and macroalbuminuria, who can change to a more soy-based source of protein in order to improve the cardiovascular disease risk factors but proteinuria is not altered [175].

4.4 Soy isoflavones and osteoporosis

The connection between soy consumption and bone health has emerged with epidemiologic studies, which found that Asian women have a lower hip fracture incidence in the elderly compared to Caucasian women. Later, it was confirmed that consumption of soybean and soy-based products, much higher among Asians, could potentially lower the bone loss rate and decrease the risk of fracture [176].

To date, the exact effects of dietary soy isoflavones on osteoporotic bone loss remain inconclusive, and results vary from study to study. Most studies, performed in vitro or using animal models, have found an inverse relation between the consumption of soy isoflavones and the percentage of bone loss. As an example, genistein was shown to reduce biochemical markers of bone metabolism, to prevent trabecular bone loss, and affect thyroid follicular cells in a male rat model of osteoporosis [177].

In humans, a post-hoc analysis of a multicenter randomized controlled trial suggested that genistein may be useful not only in postmenopausal osteopenia, but also in osteoporosis. Also, genistein has possible implications for the reduction of fracture risk in postmenopausal women with osteoporosis. These effects seem to be time-dependent and a long-term intake of genistein will produce ongoing effects on bone health [178].

The exact regulating model of soy isoflavones is still unclear, but mechanisms usually imply stimulation of bone formation and/or inhibition of bone resorption. Specifically, genistein was found to retard bone resorption by decreasing the viability of 1,25-dihyroxyvitamin D-induced osteoclasts. Other mechanisms implied enhanced bone formation by increasing serum osteocalcin concentration, femoral insulin-like growth factor 1 mRNA transcription, and serum alkaline phosphatase activity [176].

However, clinical trials outcomes are still conflicting and more well-designed studies are warranted to delineate the underlying mechanisms, the efficacy, and safety of soy isoflavones in osteoporosis. Perhaps due to these current uncertainties, the National Center for Complementary and Integrative Health (NCCIH) declared that soy isoflavone combinations do not lower the rate of bone loss in Western women during or after menopause [179].

4.5 Soy isoflavones and menopausal symptoms

The use of soy-based foods or soy supplements in alleviating menopausal symptoms such as hot flashes, night sweats, and vaginal dryness has long been a controversial subject. A systematic review and meta-analysis published in 2016 has shown that individual phytoestrogen interventions such as dietary and supplemental soy isoflavones were associated with improvement in daily hot flashes and vaginal dryness score, but no significant reduction in night sweats. However, the study concludes that further rigorous studies are needed to determine the exact association of plant-based and natural therapies with menopausal health [180]. Also, a recent analysis concluded that frequent consumption of soy products (e.g., soy beans, tofu and tempeh), but not soy milk, may be associated with a reduced risk of subsequent vasomotor menopausal symptoms [181]. In contrast, a Cochrane systematic review determined that there is no conclusive evidence that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women. Still, the study admits that genistein concentrates might pose beneficial effects, which should be further investigated [182].

The 2011 North American Menopause Society report on the role of soy isoflavones in menopausal health has concluded that initial treatment with soy-based isoflavones is reasonable for stressful vasomotor symptoms in postmenopausal women. The starting isoflavone dose should be 50 mg/day or higher, for at least 12 weeks. Supplements providing higher proportions of genistein or S(Y)-equol may provide more benefits. If a woman responds to isoflavone supplementation, treatment can continue with monitoring for side effects, but if a woman does not respond after 12 weeks, other treatment options should be discussed. The report also emphasizes on the urge of larger clinical studies aimed to investigate the exact role and mechanisms of isoflavones in postmenopausal women [183].

Advertisement

5. Polysaccharides’ contribution to health

Polysaccharides are natural polymers, found in various plants, algae, animals, and microorganisms. These polymers have exceptional properties and essential roles to sustain life. They are an important class of polymeric molecules composed of long chains of monosaccharide units bound together by glycosidic linkages [184]. General classification of polysaccharides is highly diverse; they are classified in different ways, based on their composition, function, and origin [185].

Therefore, an overview of the main polysaccharides, including their potential food and medical applications, is presented in Table 2 . Depending on the single sugar moieties (glucose, galactose, fructose, mannose), polysaccharides are classified in two groups: (1) homo-polysaccharides, which contain only one kind of polymerized sugar unit like starch, xylan, galactan, and froctan, and (2) hetero-polysaccharides, containing two or more kinds of sugar units such as pectin [186]. Polysaccharides, in many forms, play a central role in all living organisms for supply and storage of energy and/or structural integrity and protection of cells. Polysaccharide-based substances are increasingly used in health and cosmetic products manufacturing, food and feed production, and for obtaining cellulose-derived materials [187].

Polysaccharides Major sources Applications in health care Ref.
Starch (amylose/amypectin) Cereals, tubers, legumes Starch esters—matrix former in capsules for medical application
Maintaining human colonic function and preventing colonic disease
[189]
[188]
[186]
[185]
[187]
[198]
[190]
Cellulose Fungi, algae, fruit and vegetables Oxidized cellulose and regenerated cellulose are widely used as excellent hemostatic materials in various surgical operations and postsurgical adhesion prevention layers
Antitumor, immunostimulant, wound healing, and adhesion—prevention properties
Drug delivery systems
Inulin Chicory root, wheat, onion, garlic Hypolipidemic effects, prebiotic properties which influence gut microbiota
Reduces the plasma total cholesterol, LDL-cholesterol, triglycerides, and increases HDL-cholesterol concentrations
Decreases adipose tissue pro-inflammatory cytokines
Pectins Citrus peel and apple pomace
Spruce bark, mango waste
Gelling and thickening agents
In the pharmaceutical industry, as an excipient due to its non-toxicity
Specific drug delivery
Immunomodulating activities
In tissue engineering applications for bone cells culture
Xylans Beechwood
Perennial plants, fruit, legumes, and nuts
Adsorption, separation, and drug release applications
Wound dressing and antimicrobial agents
Anticoagulant properties, anti-inflammatory and anticancer effects
Immunomodulating activity
Alginate Brown seaweed Cartilage regeneration agent
Microencapsulation agent
Drug delivery system, bionanoreactors, nanofiltration, and biosensors
Chitin/chitosan Shells of crabs and shrimp, cuticles of insects Target drug delivery
In oral administration for lowering serum cholesterol concentration and hypertension
Orthopedic/periodontal materials, wound-dressing materials, tissue engineering
Drug delivery systems
Hemostatic action, anti-inflammatory effect, antitumoral antibacterial, and fungicidal properties
Antibacterial coating
(Galacto) glucomannans Guar, locust, and carob beans (seeds), fungi and alga, spruce and Aloe vera Thickeners and stabilizers agents
Drug delivery system
Anticoagulant and antithrombotic drugs
Immunomodulating and radical-scavenging activities
Xyloglucan Tamarind seed and most land plant Hypocholesterolemic and hypotriglyceridemic effects
Antitumor activity
Drug delivery system
Gelling and thickening agents

Table 2.

Main groups of polysaccharides, their origin and applications.

Recently, there has been an increased interest for polysaccharides use in various novel applications due to their biocompatibility, biodegradability, non-toxicity, and several specific therapeutic activities [188]. The relationships between polysaccharides, the effects of processing on their structures and interactions, and their behavior in the gastrointestinal tract are crucial for elucidating the relationships between diet and health [189]. Many foods contain a great number of polysaccharides that cannot be completely digested by the digestive system. These indigestible polysaccharides can be called dietary fibers [186]. The class of polysaccharides such as pectin, inulin, and gums are able to slow the food movement in the digestive tract and to slow the sugar absorption from food into blood. The specific action of polysaccharide at digestive tract is given by the fermentable process. Prebiotics are selectively fermented ingredients that result in specific changes of the gastrointestinal microbiota. They improve the mucosal barrier function of the intestine by reducing the expressions of pro-inflammatory cytokines [190].

Therefore, regular consumption of polysaccharides is suggested to beneficially enhance the gut physiology and the metabolic balance by influencing metabolic functions [185]. Intestinal microbiota degrades the polysaccharides to produce metabolites and many intestinal bacteria can use these polysaccharides as unique carbon sources during the fermentation process. An in vitro study, which simulated the human colonic fermentation and used two types of indigestible polysaccharides (apple pectin and inulin) as energy sources to three different human bowel microorganisms, showed that the low degree of polymerized inulin positively modulated the intestinal microbiota and improved the flora diversity [186]. However, pectin may also treat or prevent several diseases/disorders such as intestinal infections, atherosclerosis, cancer, and obesity. The oral administration of β-glucan reduced the intestinal inflammation levels and exerted a protective effect on other intestinal diseases and symptoms, especially celiac disease and constipation [191].

Incidence of inflammatory bowel disease has increased considerably in recent years. Therefore, the development of a new adjuvant therapy strategy that may involve natural sources such as dietary modifications is a challenging task [190]. Non-starch polysaccharides such as pectin, cellulose, hemicellulose, β-glucan, pentosane, and xylan are selected targets to reduce the incidence of inflammatory bowel disease, due to the resistance to hydrolyzation by endogenous digestive enzymes of human [192]. The inflammatory symptoms were decreased after the oral administrations of a guar gum or partially hydrolyzed guar gum mixture, a pectin-type polysaccharide; also, the bowel movement, stool consistency, the abdominal pain and diarrhea were improved [186, 193].

Current research shows that the immune-stimulating and immune-modulating functions [194, 195] of polysaccharides; these polysaccharides are called bioactive polysaccharides, they can also stimulate the immune system against cancer cells by increasing immunoglobulin. [186]. The apple-derived pectin is one of the polysaccharides that have been reported to ameliorate metabolic syndrome, and it reduces body weight and the excessive accumulation of fat. Also, the exopolysaccharides isolated from Kefir grains present the same effects as pectin. [186]. Studies have shown that moderate intakes of dietary fiber like polysaccharides can effectively lower risks for developing diabetes [188]. Diabetes mellitus is a chronic metabolic disease characterized by dysfunctions of carbohydrate, lipid, and [A1] lipoprotein metabolism, which affects approximately 4% of population worldwide and is expected to increase in next decades [186, 196]. Oral administration of β-D-glucans and other soluble non-starch polysaccharides, such as arabinoxylans, had anti-diabetic activities. The major effect of soluble non-starch polysaccharides in slowing glucose absorption is therefore of considerable benefit in terms of diabetes risk and management but also has implications for overall starch digestion [197]. In recent decades, new exploitation of polysaccharides and their derivatives focused on tissue engineering applications, such as biological signaling, cell adhesion, cell proliferation, cell differentiation, and cell responsive degradation. The obtained results showed that a variety of polysaccharides, such as alginate, chitin/chitosan, cellulose and starch and their derivatives, have been developed as biomaterials for tissue engineering applications. For example, chitin/chitosan possesses the requisite properties to act as a scaffold for tissue engineering, regarding their degradability, immunogenicity, and mechanical strength [188].

5.1 Effects of processing on polysaccharides structure and composition

In the initial processing stage, there are several factors that may trigger important modifications of polysaccharide properties. A careful attention paid to these factors is essential in establishing the polysaccharides use in food and biomedical applications. Mechanical fractionation has action on crystalline structure of starch. Dehulling and milling of cereal grains and peeling and chopping of potatoes cause physical damage to a proportion of starch granules. However, this type of starch damaged possesses a water absorption capacity 10 times greater than native starch and it is more prone to gelatinization with implications for end-use properties and digestion [189, 199].

Thermal degradation has an important action with respect to dynamic distribution of polysaccharides’ molecular weight. High temperature accelerated the degradation of high-molecular weight polysaccharides to low-molecular weight oligosaccharides and monosaccharide. Thermal processes induce two different major reaction pathways, such as the Maillard reaction, which takes place in the presence of amino acids, and caramelization, that occurs when simple sugars are heated at high temperatures [200, 201]. The predominant products of thermal decomposition of pure starch in toasted bread are the dehydrated oligomers of glucose and individual molecules of dehydrated glucose, which are involved in the Maillard reaction [189]. However, in the case of starch, the thermal decomposition showed no significant relationship between microstructure (crystallinity, granule size) and the thermal degradation process [189, 202]. Heating to higher temperatures of β-glucan solutions induces depolymerization. Similarly, β-glucan in food products that are heat treated at higher temperatures (100) has been shown to become depolymerized as a result of the processing, which was also interpreted to influence their beneficial health effects [189, 203]. It should be noted that many dietary products containing polysaccharides are processed by thermal treatment, and the chemical structure of the carbohydrates is dramatically altered by heat treatment [203, 204]. The main effect of physical modification is to truncate the original polysaccharide backbone to get fragments with lower molecular weights and only cause some conformational changes.

Microwave exposure could degrade polysaccharide structure, and thus increase solubility and biological activity. Microwave heating is described as more homogeneous, selective, and efficient as compared to conventional heating, resulting in faster reactions with fewer or no side products. The polysaccharide degradation in a microwave oven is generated by the interaction between electromagnetic field and chemical constituents of polysaccharide, due to molecular vibration and intense friction [205].

New applications of microwave heating were used in the grafting modifications of polysaccharides, with the precise control of the graft polymer. Microwave irradiation can be a method for the development of valuable products with tailor made properties [206]. It has been shown that the properties of microwave-synthesized graft polysaccharides are normally superior to the derivatives synthesized conventionally, but it still requires very careful control of reaction parameters to obtain polysaccharides with suitable properties and grafting efficiency.

Microwave application has advantages of economical usage of time and power energy, and also, it is easy to operate [205, 206, 207]. Another type of physical treatment is application of ultra-high pressure widely used in food and medicine. Depolymerization is the main effect caused by the application of high pressure treatment on polysaccharides; it was shown that the effect of high pressure was found to be dependent on the structure and conformation of the polysaccharides and strongly on their structure: globular branched structures similar to gum arabic are nearly unaffected, while linear stiff polymers undergo depolymerization [208, 209].

Gum arabic was found not to be affected by the high pressure treatment, probably because of its branched and globular structures [208]; the same effect was also identified on cellulose [210]. Radiation processing of natural polymers has received much less attention over the years because most of the natural polymers undergo chain scission reaction when exposed to high-energy radiation and because of the difficulty in processing natural polymers in various forms and sizes [211]. There have been many reports about the effects of gamma irradiation on the degradation of polysaccharides, including the treatments of chitosan [211], cellulose [212], β-glucan [213], and so on. Gamma irradiation improved the solubility and decreased the viscosity of β-glucan by the radiolysis of the glycosidic bonds, and this effect was dependent upon the absorbed dose. Therefore, gamma irradiation could be used in commercial processes as an effective method to resolve the physical problems involved in the use of β-glucan with high viscosity and low solubility [213]. Regarding the effect of gamma irradiation on starch, the result showed increased water solubility and water absorption and, also, an increase of antioxidant activity [205].

Besides new technologies based on polysaccharides, irradiation can be used for the decontamination of food and food additives as well as for the sterilization of materials containing polysaccharides. The irradiation of polysaccharide-containing systems has already found or has potential to find use in plastics technology, in nanotechnology, in medicinal and pharmaceutical areas, in the food industry, and in the chemical and other technical industries [214].

Advertisement

6. Marine bioactive compounds: functional properties

Seafood products are considered inherently functional due to their many valuable compounds and bioactive molecules possessing health benefits [215, 216]. Bioactive components can be isolated from seafoods and seafood co-products and further added to various foods to enhance their functionality in terms of human health [217]. According to recent studies, biologically active protein and lipid compounds can be extracted from fish and other marine organisms like sponges, tunicates, sea hares and slugs, soft corals, bryozoans, as well as marine animals and seafood side streams.

The bioactives with strong health-promoting effects include vitamins, fish muscle proteins, marine peptides and depsipeptides, collagen and gelatin, fish oil, PUFAs, etc. [218, 219, 220]. Some of these bioactive components are of particular pharmaceutical and nutraceutical interest due to claimed health benefits [221]. A big part of marine bioactive compounds has been isolated, characterized, and further modified for the development of analogs with improved activities [222, 223, 224].

Bioactive peptides extracted from marine organisms and seafood by-products have been reported to possess various activities, including antimicrobial, immunomodulatory, antithrombotic, antioxidant, mineral binding, hypocholesterolemic, and antihypertensive actions [225]. These bioactive compounds can also be used in diverse therapeutic applications for the prevention and/or treatment of chronic diseases, as well as modulation and improvement of physiological functions [224]. The following extraction methods have been mainly used to obtain lipid and protein bioactive ingredients from seafood sources: solvent extraction, heating/cooking, enzymatic hydrolysis, and microbial fermentation of marine proteins. However, heating and enzymatic hydrolysis are the most preferred methods in the food and pharmaceutical industries due to lack of residual organic solvents and/or toxic chemicals in the end products [224, 226].

Fish is a rich source of valuable protein and lipid components worldwide [227]. Moreover, fish muscle proteins possess the potential of providing bioactive peptides to the food, pharmaceutical, and nutraceutical industries [228]. Other marine sources for bioactive peptides include sponges, ascidians, tunicates, and mollusks. A number of these marine species have been studied in depth for presence of bioactive peptides and depsipeptides, including clinical assays, and an extensive group of bioactive peptides has been found [224].

The reported group of bioactive peptides includes compounds with antitumor activities such as Aurilide from tunicate Dolabella auricularia [229], Didemnin from tunicate Trididemnum sp. [230], Homophymines from sponge Homophymia sp. [231], Trunkamide A from ascidian Lissoclinum sp. [232], and Keenamide A from mollusk Pleurobranchus forskalii [233]. Antiproliferative bioactivities were found in Mollamide from ascidian Didemnum molle [234] and other bioactive peptides such as Geodiamolide H, Phakellistatins, and Jaspamide isolated from sponges of the genus Geodia sp. [235], Phakellia carteri [236], and Jaspis sp. [237], respectively. The most preferred method to extract bioactive peptides is enzymatic hydrolysis. Enzymatic hydrolysis results in several peptides with different bioactivities, which offers a huge potential to use them in pharmaceuticals and nutraceuticals.

The biological activity of small peptides present in protein hydrolysates depends on their molecular weight and amino acid sequences [238]. A fractionation step is generally applied to crude hydrolysates to separate individual peptides by using different techniques, such as gel permeation chromatography or reverse-phase high-performance liquid chromatography (RP-HPLC) [219, 239]. Bioactive peptides recovered by enzymatic hydrolysis are usually consisted of 2–20 amino acid residues, and their activities are influenced by their amino acid composition and sequence. A high number of hydrolyzed proteins extracted from seafood by-products have been assayed for various bioactivities, such as antioxidant, antiproliferative, antitubulin, and cytotoxic activities [225]. These biological activities can possess anticancer potential, providing the opportunity to use the recovered peptides in cancer therapy [224]. As mentioned above, seafood side streams and co-products resulting after fish processing are rich sources of valuable protein ingredients for further exploitation in the production of new products such as feed, functional foods, cosmetics, and nutraceuticals [240].

Various seafood rest raw materials such as heads, skin, cut-offs, frame, bone, and viscera can be utilized to isolate a number of bioactive protein ingredients [241]. Fish rest raw material resulting after filleting contains high amounts of high-value proteins containing all essential amino acids. Enzymatic hydrolysis can be used to obtain fish protein hydrolysates (FPH) for further isolation of bioactive peptides. FPH have been shown to contain peptides with, for example, immunostimulating and blood pressure-lowering (ACE-inhibiting) properties, in addition to antiproliferative (antimicrobial), anticoagulant, and immunomodulatory effects. These peptides may be used in novel formulations of nutraceuticals and cosmeceuticals [242]. Bioactive peptides generally include 3–20 amino acid residues and their biological activities are based on their molecular weights and amino acid sequences.

Fish bones and skin are a good source of gelatin and collagen. Collagen finds wide applications in pharma/nutra/cosmeceutical, biomedical, tissue engineering, and film/coating industries either as collagen polypeptide/peptide or gelatin (denatured form of collagen consisting of low-molecular weight peptides and proteins) [243, 244, 245]. Gelatin is formed from collagen polypeptide chains by partial thermal hydrolysis. Thus, gelatin is a denatured form of native collagen. Gelatin has been reported to possess unique rheological properties including gel strength, thermal stability, and viscoelastic properties [246]. It is widely applied in the food industry as gelling agent to improve the texture, water-holding capacity, and stability for certain food products. Gelatin can be also used as carrier of active substances such as antimicrobials, antioxidants, flavors, and colors, for production of coatings, as well as microencapsulation of bioactive compounds in pharma-/nutraceuticals [247].

Nevertheless, collagen is characterized by greater mechanical strength, higher enthalpy and resistance to protease hydrolysis, as well as more dense structure with more rigid and firm fibril networks compared to gelatin [248]. Collagen can be successfully used both as a drug carrier and in the treatment of hypertension and pain associated with osteoarthritis, in tissue engineering and inhibition of angiogenic diseases, as well as in production of wound dressings and skin substitutes [249]. Marine collagen and gelatin have attracted a great interest for their unique properties and potential applications in pharma/nutraceuticals, cosmeceuticals, and food manufacturing. The extraction and characterization of collagen and gelatin has been reported from different fish species, including hake [250], ocellate puffer fish [251], Pacific [252], Baltic cod [253], logbarbel catfish [248], Jumbo squid [254], golden goatfish [254], red tilapia and barramundi [255], rainbow trout [256], albacore tuna [257], African catfish [258], Atlantic salmon [259], channel catfish [260], bluefin tuna [261], and others.

As mentioned before, using specific physical and chemical pre-treatments (heat, enzymes, etc.) followed by tailored extraction procedures, seafood rest raw materials might provide bioactive protein components (protein hydrolysates, bioactive peptides, collagen/gelatin, etc.). Some peptide fractions can be individually isolated from hydrolysates using tailored biotechnological processes for potential applications in various industries. Recovery and separation of low- and high-weight peptides from different protein fractions resulting from seafood co-products could provide valuable streams for exploitation in different sectors. The complete exploitation of seafood side streams is often compromised by their high susceptibility to microbiological spoilage and oxidation, as well as proliferation of pathogenic agents. In addition, despite a potential to recover bioactive proteins from seafood side streams, there is still a challenge to meet the growing consumer demands for sensory characteristics of the recovered protein ingredients and foods prepared thereof.

Moreover, a crucial step in the transformation of seafood co-products into new protein ingredients is the use of technological processes that permit the production of microbiologically and biochemically stable ingredients, while minimizing loss of bioactive, nutritional, and functional properties. Marine lipids play role of valuable components of cell membranes, while being carriers of fat-soluble vitamins and energy providers. They also serve as an excellent source of polyunsaturated fatty acids (PUFAs) such eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are part of the omega-3 group. These fatty acids cannot be found in plant sources. Plant oils contain another type of omega-3 fatty acids called α-linolenic acid, which is a metabolic precursor of the omega-3 fatty acids found in fish and fish oils [262].

Although human body is able to convert dietary α-linolenic acid into eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids found in marine lipids, this conversion cannot be considered efficient for modern consumers proffering typical Western diet rich in saturated fat and omega-6 fatty acids [263]. Thus, consuming foods rich in α-linolenic acid, our tissues are exposed to very little action of EPA and DHA. Regardless the fact that some biological activity has been associated with the action of plant-derived omega-3 fatty acids, the main health benefits are attributed to the conversion of α-linolenic acid to EPA and DHA [262]. Omega-3 fatty acids are mainly found in the body of fatty fish (salmon, mackerel, herring, tuna, etc.), the liver of white lean fish (cod), and the blubber of marine mammals feeding on phytoplankton or other aquatic species containing these fatty acids [220]. Microalgae play role of the main generators and suppliers of omega-3 fatty acids to the whole marine ecosystem [264]. In addition, omega-rich algal oils can be obtained via fermentation processes or from kelp and seaweed [265] and are currently in huge demand due to a number of positive effects and industrial applications [266] in the food and feed industries, fisheries, aquaculture, agriculture, pharmacy, and cosmetics. The omega-3 fatty acids that are highly sought after by the nutraceutical and pharmaceutical industries are cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA).

They are essential components of a healthy diet and are indispensable for the proper development and function of the nervous system, brain, and eyes, as well as serve as a preventative for cardiovascular diseases and inflammation [267, 268]. Their health benefits also include lowering of triacylglycerols and reducing the incidence of non-communicable diseases such as metabolic syndrome, type-2 diabetes, cancer, arrhythmias, as well as inflammatory diseases and immunomodulatory effects [220]. Other beneficial effects ascribed to PUFAs include antithrombotic, hypolipidemic, antiarrhythmic, and antihypertensive properties [269, 270]. The first studies regarding the health benefits of PUFAs have investigated the diet of the Eskimo population of Greenland, characterized by high intake of seafood rich in omega-3 fatty acids. The research performed by Bjerregaard et al. in these individuals has revealed a correlation between the high consumption of PUFA-rich foods and the low incidence of cardiovascular diseases [271]. These pioneer investigations became a starting point for further epidemiological and interventional studies on the cardioprotective role of omega-3 fatty acids [272]. PUFAs contribute to the formation of special biologically active compounds called eicosanoids, which include prostaglandins, leukotrienes, and thromboxanes [273]. Lipoxins, resolvins, and neuroprotectins with strong anti-inflammatory effects are also derived from EPA and DHA [274].

In addition, the products of PUFA metabolism participate in the maintenance of cell membrane architecture [275] and support homeostasis and vasoconstriction [276]. The cell membrane is exposed to various positive modifications under the influence of the long hydrocarbon chains and double bonds in EPA and DHA. These PUFAs enhance fluidity of the cell membrane [277] and change the distribution and size of lipid rafts in aortic endothelial cells [278]. A number of research investigations have also revealed that PUFAs can successfully prevent weight gain [279, 280]. Omega-3-rich marine lipids were shown to reduce the activity of some nuclear receptors, among which is peroxisome proliferator-activated receptor γ (PPAR γ) regulating the transcription of several genes responsible for lipid metabolism. Thus, low PPAR γ activity leads to low fat deposits in the adipose tissue and the brain, decreasing the stimulus to consume fat-rich products [281, 282]. The main challenge associated with EPA and DHA is that these omega-3 fatty acids are highly polyunsaturated and readily undergo oxidation [283, 284]. Out of the biological context, DHA and EPL are highly sensitive to oxidation by molecular oxygen present in air due to their polyunsaturated nature. In the enzymatic path of PUFA oxidation, fatty acid oxygenases control the formation of fatty acid-peroxyl radicals. Thus, peroxyl radicals generated during the reaction of PUFAs with molecular oxygen upon biosynthesis of fatty acid peroxides as intermediates in autacoid formation are instantly reduced within the enzyme active site to form the corresponding peroxide. However, in the non-enzymatic path of PUFA oxidation, a temporarily generated peroxyl radical targets at abstracting a hydrogen atom from any of the nearby hydrogen-donating molecules. This molecule can be an antioxidant or a nearby-situated PUFA molecule if the concentration of reduced antioxidants is low enough to effectively scavenge peroxyl radicals formed [285]. At later stages of non-enzymatic peroxidation reactions, secondary lipid oxidation products are formed in the chain reactions involving fatty acid peroxides.

Generation of secondary lipid oxidation products depends on the initial formation and further consumption of fatty acid peroxides. Alkoxy radicals generated from the previously formed peroxides can be involved in reactions with conjugated dienes derived upon earlier hydrogen abstraction-promoted double bond rearrangements, thus fostering the formation of chain-shortened α, β-unsaturated aldehydes through cleavage of the fatty acid chain [285]. The entire description of the free radical-mediated oxidation reactions involving PUFAs is extremely complex and depends on many factors [286]. Thus, marine lipids exposed to oxygen are subjected to fast quality deterioration due to the free radical-mediated propagation of PUFA peroxidation. PUFA-rich marine oils are highly prone to oxidation under ambient conditions. Nevertheless, the oxidation rate can be significantly slowed down by adding and maintaining sufficiently high concentrations of antioxidants and limiting exposure to external factors such as air, heat, and light [287]. According to quality requirements established by GOED (Global Organization for EPA and DHA Omega-3 s), omega-3 PUFA-rich oils should comply with the following limits: 1) on primary oxidation: peroxide value (PV) less than 5 meq O2/kg and 2) secondary oxidation: para-anisidine value (p-AV) less than 20, as well as a combined measurement of total oxidation comprising both the level of primary and secondary oxidation (TOTOX < 26) [288].

Advertisement

7. Conclusions

Today, food market is richer than ever and consumers have begun to pay more and more attention to what they consume. In this light, functional foods, also known as medicinal or pharmacological foods, have experienced a tremendous growth, as various health-related claims are dispatched on their label. One of the most appealing groups of functional foods is represented by probiotics. Although there are numerous studies that highlight good viability profiles with excellent sensorial properties of a wide range of probiotic functional foods, an obvious conclusion has not yet been drawn. Therefore, more in vivo studies are needed to establish a concrete relation between probiotic functional foods intake and prevention, amelioration, or treatment of specific disorders (e.g., colon cancer). In case of secondary metabolites, their pharmacological activities have been widely demonstrated in numerous researches. Apparently, these functional molecules can reduce the incidence of developing chronic degenerative diseases, stroke, and cancer. A distinctive class of secondary metabolites, soy isoflavones provide a series of health benefits such as chemoprotective and chemotherapeutic effects, help reduce the menopause-related symptoms, prevent postmenopausal osteoporosis, or reduce the risk of coronary heart diseases.

Another important group of functional biomolecules is represented by polysaccharides. Several studies have found a positive interaction between polysaccharide-rich diet and metabolic health in the sense of reducing obesity, diabetes, and cardiovascular diseases, and also an inverse relationship between dietary fiber intake and body weight.

A similar positive impact on human health was observed after increasing the consumption of seafood and enrichment of food products with bioactive components extracted from fish, shellfish, seaweed, and seafood co-products. Therefore, for a healthy diet, it is extremely important to promote the consumption of seafood products, while reducing the consumption of high-sugar and high-fat foods.

All data presented herein aim to provide current, precise, and relevant information for nutritionists, education specialists, public health organizations, different organizations (prevention education programs), policy makers, and food industries. They represent key players that can influence consumers to make healthier food selections through labeling and nutrition information on food and beverages. Only in this way, customers will benefit from balanced and healthy diets that are essential to prevent diseases and illnesses.

Advertisement

Acknowledgments

This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS/CCCDI–UEFISCDI, project number PN-III-P2-2.1-CI-2018-1462, within PNCDI III. Authors L.C. Salanță and A. Uifălean contributed equally to this work.

Advertisement

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1. Fărcaş AC, Socaci SA, Mudura E, Dulf FV, Vodnar DC, Tofană M, et al. Exploitation of brewing industry wastes to produce functional ingredients. In: Kanauchi M, editor. Brewing Technology. Rijeka, Croatia: InTech; 2017. pp. 137-156
  2. 2. Hong YC. After the end of chronic disease. In: Hong YC, editor. The Changing Era of Diseases. London, UK: Academic Press; 2019. pp. 145-174
  3. 3. Hunter DC, Jones VS, Hedderley DI, Jaeger SR. The influence of claims of appetite control benefits in those trying to lose or maintain weight: The role of claim believability and attitudes to functional foods. Food Research International. 2019;119:715-724
  4. 4. Urala N, Lähteenmäki L. Reasons behind consumers’ functional food choices. Nutrition & Food Science. 2003;33(4):148-158
  5. 5. Khedkar S, Carraresi L, Bröring S. Food or pharmaceuticals? Consumers’ perception of health-related borderline products. PharmaNutrition. 2017;5(4):133-140
  6. 6. Mahabir S. Methodological challenges conducting epidemiological research on nutraceuticals in health and disease. PharmaNutrition. 2014;2(3):120-125
  7. 7. Kendilci E, Kendilci K, Gunes G. Assessment of awareness, knowledge levels and consumer perception of students of health high school towards functional foods. Medicine Science International Medical Journal. 2017;6(4):1
  8. 8. Rincón-León F. Functional foods. In: Caballero B, editor. Encyclopedia of Food Sciences and Nutrition. 2nd edition. London, UK: Academic Press; 2003. pp. 2827-2832
  9. 9. Mak TN, Caldeira S. The role of nutrition in active and healthy ageing: For prevention and treatment of age-related diseases: Evidence so far. Publications Office of the European Union. 2014. Available from: https://publications.jrc.ec.europa.eu/repository/bitstream/JRC90454/lbna26666enn.pdf [Accessed: 09 February 2020]
  10. 10. Mascarello G, Pinto A, Parise N, Crovato S, Ravarotto L. The perception of food quality. Profiling Italian consumers. Appetite. 2015;89:175-182
  11. 11. Zeeshan Zafar M, Hashim A, Halim F. Consumer’s perception toward health claims for healthy food selection. Journal of Scientific Research and Development. 2016;3(1):57-67
  12. 12. Sadilek T. Perception of food quality by consumers: Literature review. European Research Studies Journal. 2019;22(1):52-62
  13. 13. Fărcaş AC, Socaci SA, Dulf FV, Tofană M, Mudura E, Diaconeasa Z. Volatile profile, fatty acids composition and total phenolics content of brewers’ spent grain by-product with potential use in the development of new functional foods. Journal of Cereal Science. 2015;64:34-42
  14. 14. Salanţă LC, Tofană M, Socaci S, Mudura E, Pop C, Pop A, et al. The potential of medicinal plants in developing functional foods. Hop and Medicinal Plants. 2014;22(1-2):44-50
  15. 15. Țiplea R, Suharoschi R, Leopold L, Fetea F, Socaci SA, Vodnar DC, et al. Alfalfa leaf powder and its potential utilisation in raw vegan chocolate. Bulletin of the University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca Food Science and Technology. 2019;76(1):76-79
  16. 16. Pop O, Dulf F, Cuibus L, Castro-Giráldez M, Fito P, Vodnar D, et al. Characterization of a sea buckthorn extract and its effect on free and encapsulated lactobacillus casei. International Journal of Molecular Sciences. 2017;18(12):2513
  17. 17. Socaci SA, Fărcaş AC, Diaconeasa ZM, Vodnar DC, Rusu B, Tofană M. Influence of the extraction solvent on phenolic content, antioxidant, antimicrobial and antimutagenic activities of brewers’ spent grain. Journal of Cereal Science. 2018;80:180-187
  18. 18. Pintea A, Rugină D, Diaconeasa Z. Pharmacologically active plant-derived natural products. Smart Nanoparticles for Biomedicine. 2018;1:49-64
  19. 19. Vlaic RA, Mureşan V, Mureşan AE, Mureşan CC, Păucean A, Mitre V, et al. The changes of polyphenols, flavonoids, anthocyanins and chlorophyll content in plum peels during growth phases: From fructification to ripening. Notulae Botanicae Horti Agrobotanici Cluj-Napoca. 2018;46(1):148-155
  20. 20. Vlaic RA, Mureșan AE, Mureșan CC, Petruț GS, Mureșan V, Muste S. Quantitative analysis by HPLC and FT-MIR prediction of individual sugars from the plum fruit harvested during growth and fruit development. Agronomy. 2018;8(12):306
  21. 21. Mohanty D, Misra S, Mohapatra S, Sahu PS. Prebiotics and synbiotics: Recent concepts in nutrition. Food Bioscience. 2018;26:152-160
  22. 22. Fazilah NF, Ariff AB, Khayat ME, Rios-Solis L, Halim M. Influence of probiotics, prebiotics, synbiotics and bioactive phytochemicals on the formulation of functional yogurt. Journal of Functional Foods. 2018;48:387-399
  23. 23. Ares G. Non-sensory factors which influence choice behavior of foods that have a positive effect on health. In: Handbook of Behavior, Food and Nutrition. New York, NY: Springer; 2011. pp. 757-770
  24. 24. Fiszman S, Carrillo E, Varela P. Consumer perception of carriers of a satiating compound. Influence of front-of-package images and weight loss-related information. Food Research International. 2015;78:88-95
  25. 25. Ježovičová K, Turčínková J, Drexler D. The influence of package attributes on consumer perception at the market with healthy food. Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis. 2016;64(6):1919-1926
  26. 26. Ordabayeva N, Srinivasan R. The effects of salience of the sound of food on consumption. Appetite. 2019;138:260-268
  27. 27. Horská E, Ürgeová J, Prokeinová R. Consumers’ food choice and quality perception: Comparative analysis of selected Central European countries. Agricultural Economics. 2011;57(10):493-499
  28. 28. Iriondo-Dehond M, Miguel E, Del Castillo MD. Food byproducts as sustainable ingredients for innovative and healthy dairy foods. Nutrients. 2018;10(10):1-24
  29. 29. Haasova S, Florack A. Practicing the (un)healthy = tasty intuition: Toward an ecological view of the relationship between health and taste in consumer judgments. Food Quality and Preference. 2019;75(September 2017):39-53
  30. 30. Lusk JL. Consumer perceptions of healthy and natural food labels. A Report Prepared for the Corn Refiners Association. 2019. Available from: https://static1.squarespace.com/static/502c267524aca01df475f9ec/t/5c4df49440ec9a53af435ab4/1548612761167/report_revised.pdf. [Accessed: 09 February 2020]
  31. 31. Cencic A, Chingwaru W. The role of functional foods, nutraceuticals, and food supplements in intestinal health. Nutrients. 2010;2(6):611-625
  32. 32. Santeramo FG, Carlucci D, De Devitiis B, Seccia A, Stasi A, Viscecchia R, et al. Emerging trends in European food, diets and food industry. Food Research International. 2018;104:39-47
  33. 33. Coughlin JF, Pope J. Innovations in health, wellness, and aging-in-place. IEEE Engineering in Medicine and Biology Magazine. 2008;27(4):47-52
  34. 34. Gray J, Armstrong G, Farley H. Opportunities and constraints in the functional food market. Nutrition & Food Science. 2003;33(5):213-218
  35. 35. Bleiel J. Functional foods from the perspective of the consumer: How to make it a success? International Dairy Journal. 2010;20(4):303-306
  36. 36. Irene Goetzke B, Spiller A. Health-improving lifestyles of organic and functional food consumers. British Food Journal. 2014;116(3):510-526
  37. 37. Kraus A. Factors influencing the decisions to buy and consume functional food. British Food Journal. 2015;117(6):1622-1636
  38. 38. Laroche M, Bergeron J, Barbaro-Forleo G. Targeting consumers who are willing to pay more for environmentally friendly products. Journal of Consumer Marketing. 2001;18(6):503-520
  39. 39. Roosen J, Bieberstein A, Blanchemanche S, Goddard E, Marette S, Vandermoere F. Trust and willingness to pay for nanotechnology food. Food Policy. 2015;52:75-83
  40. 40. Plasek B, Temesi Á. The credibility of the effects of functional food products and consumers’ willingness to purchase/willingness to pay—Review. Appetite. 2019;143:104398
  41. 41. Kaur A, Scarborough P, Matthews A, Payne S, Mizdrak A, Rayner M. How many foods in the UK carry health and nutrition claims, and are they healthier than those that do not? Public Health Nutrition. 2016;19(6):988-997
  42. 42. Benson T, Lavelle F, Bucher T, McCloat A, Mooney E, Egan B, et al. The impact of nutrition and health claims on consumer perceptions and portion size selection: Results from a nationally representative survey. Nutrients. 2018;10(5):656
  43. 43. Küster-Boluda I, Vidal-Capilla I. Consumer attitudes in the election of functional foods. Spanish Journal of Marketing—ESIC. 2017;21:65-79
  44. 44. Baboota RK, Bishnoi M, Ambalam P, Kondepudi KK, Sarma SM, Boparai RK, et al. Functional food ingredients for the management of obesity and associated co-morbidities—A review. Journal of Functional Foods. 2013;5(3):997-1012
  45. 45. GBD 2017 Diet Collaborators, Afshin A, Sur PJ, Fay KA, Cornaby L, Ferrara G, et al. Health effects of dietary risks in 195 countries, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2019;393(10184):1958-1972
  46. 46. MacKenzie D. The end of civilisation. New Scientist (1971). 2008;198(2650):28-31
  47. 47. Dixon JB. The effect of obesity on health outcomes. Molecular and Cellular Endocrinology. 2010;316(2):104-108
  48. 48. Nóvoa Medina Y, Peña-Quintana L. Growth and nutrition. In: Ferranti M, Berry EM, Anderson JR, editors. The Encyclopedia of Food Security and Sustainability. Amsterdam, The Netherlands: Elsevier; 2019. pp 353-363
  49. 49. Bartleman J. Infant and child nutrition. Medicine (Baltimore). 2019;47(3):195-198
  50. 50. Sypes EE, Parkin PC, Birken CS, Carsley S, MacArthur C, Maguire JL, et al. Higher body mass index is associated with iron deficiency in children 1 to 3 years of age. The Journal of Pediatrics. 2019;207:198-204.e1
  51. 51. World Health Organization. WHA65.6. Comprehensive implementation plan on maternal, infant and young child nutrition. 2012. Available from: https://www.who.int/nutrition/topics/WHA65.6_resolution_en.pdf [Accessed: 09 February 2020]
  52. 52. Raghupathi W, Raghupathi V. An empirical study of chronic diseases in the United States: A visual analytics approach. International Journal of Environmental Research and Public Health. 2018;15(3):431
  53. 53. Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet. 2004;364(9438):937-952
  54. 54. De Caterina R, Zampolli A, Del Turco S, Madonna R, Massaro M. Nutritional mechanisms that influence cardiovascular disease. The American Journal of Clinical Nutrition. 2006;83(2):421S-426S
  55. 55. Devore EE, Grodstein F, van Rooij FJA, Hofman A, Stampfer MJ, Witteman JCM, et al. Dietary antioxidants and long-term risk of dementia. Archives of Neurology. 2010;67(7):819-825
  56. 56. Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives. 2001;109(Suppl 1):69-75
  57. 57. Ramalingum N, Mahomoodally MF. The therapeutic potential of medicinal foods. Advances in Pharmacological Sciences. 2014;2014:354264
  58. 58. Soleymani S, Zargaran A. From food to drug: Avicenna’s perspective, a brief review. Research Journal of Pharmacognosy. 2018;5(2):65-69
  59. 59. Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, Kor NM. Functional foods and their role in cancer prevention and health promotion: A comprehensive review. American Journal of Cancer Research. 2017;7(4):740-769
  60. 60. Pramila G, Jirekar DB, Farooqui M, Naikwade SD. Biological activity of aqueous extract of some medicinal plants. Der Chemica Sinica. 2014;5(4):65-70
  61. 61. Kaczorowski J, Campbell NRC, Duhaney T, Mang E, Gelfer M. Reducing deaths by diet: Call to action for a public policy agenda for chronic disease prevention. Canadian Family Physician. 2016;62(6):469-470
  62. 62. Everitt AV, Hilmer SN, Brand-Miller JC, Jamieson HA, Truswell AS, Sharma AP, et al. Dietary approaches that delay age-related diseases. Clinical Interventions in Aging. 2006;1(1):11-31
  63. 63. Tilman D, Clark M. Global diets link environmental sustainability and human health. Nature. 2014;515(7528):518-522
  64. 64. Danneskiold-Samsøe NB, Dias de Freitas Queiroz Barros H, Santos R, Bicas JL, Cazarin CBB, Madsen L, et al. Interplay between food and gut microbiota in health and disease. Food Research International. 2019;115:23-31
  65. 65. Ding R, Goh W-R, Wu R, Yue X, Luo X, Khine WWT, et al. Revisit gut microbiota and its impact on human health and disease. Journal of Food and Drug Analysis. 2019;27(3):623-631
  66. 66. Dunne C, O’Mahony L, Murphy L, Thornton G, Morrissey D, O’Halloran S, et al. In vitro selection criteria for probiotic bacteria of human origin: Correlation with in vivo findings. The American Journal of Clinical Nutrition. 2001;73(2):386s-392s
  67. 67. Vallianou N, Stratigou T, Christodoulatos GS, Dalamaga M. Understanding the role of the gut microbiome and microbial metabolites in obesity and obesity-associated metabolic disorders: Current evidence and perspectives. Current Obesity Reports. 2019;8(3):317-332
  68. 68. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031
  69. 69. Hapfelmeier S, Lawson MAE, Slack E, Kirundi JK, Stoel M, Heikenwalder M, et al. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science (80-). 2010;328(5986):1705-1709
  70. 70. Tripathi MK, Giri SK. Probiotic functional foods: Survival of probiotics during processing and storage. Journal of Functional Foods. 2014;9:225-241
  71. 71. Granato D, Branco GF, Nazzaro F, Cruz AG, Faria JAF. Functional foods and nondairy probiotic food development: Trends, concepts, and products. Comprehensive Reviews in Food Science and Food Safety. 2010;9(3):292-302
  72. 72. Roberfroid MB. Prebiotics and probiotics: Are they functional foods? The American Journal of Clinical Nutrition. 2000;71(6):1682S-1687S
  73. 73. Coman MM, Cecchini C, Verdenelli MC, Silvi S, Orpianesi C, Cresci A. Functional foods as carriers for SYNBIO®, a probiotic bacteria combination. International Journal of Food Microbiology. 2012;157(3):346-352
  74. 74. Konar N, Toker OS, Oba S, Sagdic O. Improving functionality of chocolate: A review on probiotic, prebiotic, and/or synbiotic characteristics. Trends in Food Science and Technology. 2016;49:35-44
  75. 75. Altamirano-Fortoul R, Moreno-Terrazas R, Quezada-Gallo A, Rosell CM. Viability of some probiotic coatings in bread and its effect on the crust mechanical properties. Food Hydrocolloids. 2012;29(1):166-174
  76. 76. Pimentel TC, Klososki SJ, Rosset M, Barão CE, Marcolino VA. Fruit juices as probiotic foods. In: Grumezescu A, Holban AM, editors. Sports and Energy Drinks: Volume 7: The Science of Beverages. Cambridge, England: Woodhead Publishing Limited; 2019. pp. 483-513
  77. 77. Talebzadeh S, Sharifan A. Developing probiotic jelly desserts with lactobacillus acidophilus. Journal of Food Processing & Preservation. 2017;41(1):e13026
  78. 78. Kołożyn-Krajewska D, Dolatowski ZJ. Probiotic meat products and human nutrition. Process Biochemistry. 2012;47(12):1761-1772
  79. 79. De Vuyst L, Falony G, Leroy F. Probiotics in fermented sausages. Meat Science. 2008;80(1):75-78
  80. 80. Bambace MF, Alvarez MV, MDR M. Novel functional blueberries: Fructo-oligosaccharides and probiotic lactobacilli incorporated into alginate edible coatings. Food Research International. 2019;122:653-660
  81. 81. Saarela MH. Probiotic functional foods. In: Saarela M, editor. Functional Foods: Concept to Product. Cambridge, England: Woodhead Publishing Limited; 2011. pp. 425-449
  82. 82. McCartney AL, Wenzhi W, Tannock GW. Molecular analysis of the composition of the bifidobacterial and lactobacillus microflora of humans. Applied and Environmental Microbiology. 1996;62(12):4608-4613
  83. 83. Molin G, Jeppsson B, Johansson ML, Ahrné S, Nobaek S, Ståhl M, et al. Numerical taxonomy of Lactobacillus spp. associated with healthy and diseased mucosa of the human intestines. The Journal of Applied Bacteriology. 1993;74(3):314-323
  84. 84. Belenguer A, Duncan SH, Calder AG, Holtrop G, Louis P, Lobley GE, et al. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Applied and Environmental Microbiology. 2006;72(5):3593-3599
  85. 85. Ahmadi E, Alizadeh-Navaei R, Rezai MS. Efficacy of probiotic use in acute rotavirus diarrhea in children: A systematic review and meta-analysis. Caspian Journal of Internal Medicine. 2015;6(4):187-195
  86. 86. Marteau PR, de Vrese M, Cellier CJ, Schrezenmeir J. Protection from gastrointestinal diseases with the use of probiotics. The American Journal of Clinical Nutrition. 2001;73(2):430s-436s
  87. 87. Menees S, Chey W. The gut microbiome and irritable bowel syndrome. F1000Research. 2018;7:1029
  88. 88. Saura-Calixto F, Goñi I. Antioxidant capacity of the Spanish Mediterranean diet. Food Chemistry. 2006;94(3):442-447
  89. 89. Chimi H, Cillard J, Cillard P, Rahmani M. Peroxyl and hydroxyl radical scavenging activity of some natural phenolic antioxidants. Journal of the American Oil Chemists’ Society. 1991;68(5):307-312
  90. 90. Gülçin İ. Antioxidant activity of food constituents: An overview. Archives of Toxicology. 2012;86(3):345-391
  91. 91. Marinova EM, Yanishlieva NV. Effect of lipid unsaturation on the antioxidative activity of some phenolic acids. Journal of the American Oil Chemists' Society. 1994;71(4):427-434
  92. 92. Santos EL, Maia BH, Ferriani AP, Teixeira SD. Flavonoids: Classification, biosynthesis and chemical ecology. In: Justino GC, editor. Flavonoids - From Biosynthesis to Human Health. Rijeka, Croatia: InTech; 2017. pp. 3-16
  93. 93. Vinson JA, Su X, Zubik L, Bose P. Phenol antioxidant quantity and quality in foods: Fruits. Journal of Agricultural and Food Chemistry. 2001;49(11):5315-5321
  94. 94. Sikora E, Cieślik KT. The sources of natural antioxidants. Acta Scientiarum Polonorum, Technologia Alimentaria. 2008;7:5-17
  95. 95. Mudura E, Coldea TE, Socaciu C, Ranga F, Pop CR, Rotar AM, et al. Brown beer vinegar: A potentially functional product based on its phenolic profile and antioxidant activity. Journal of the Serbian Chemical Society. 2018;83(1):19-30
  96. 96. Kawasaki BT, Hurt EM, Mistree T, Farrar WL. Targeting cancer stem cells with phytochemicals. Molecular Interventions. 2008;8(4):174-184
  97. 97. Chen X, Dang T-TT, Facchini PJ. Noscapine comes of age. Phytochemistry. 2015;111:7-13
  98. 98. Działo M, Mierziak J, Korzun U, Preisner M, Szopa J, Kulma A. The potential of plant phenolics in prevention and therapy of skin disorders. International Journal of Molecular Sciences. 2016;17(2):160
  99. 99. Andreu L, Nuncio-Jáuregui N, Carbonell-Barrachina ÁA, Legua P, Hernández F. Antioxidant properties and chemical characterization of Spanish Opuntia ficus-indica Mill. cladodes and fruits. Journal of the Science of Food and Agriculture. 2018;98(4):1566-1573
  100. 100. Meng X-H, Liu C, Fan R, Zhu L-F, Yang S-X, Zhu H-T, et al. Antioxidative Flavan-3-ol dimers from the leaves of Camellia fangchengensis. Journal of Agricultural and Food Chemistry. 2018;66(1):247-254
  101. 101. Leong L, Shui G. An investigation of antioxidant capacity of fruits in Singapore markets. Food Chemistry. 2002;76(1):69-75
  102. 102. Frankel EN. Antioxidants in lipid foods and their impact on food quality. Food Chemistry. 1996;57(1):51-55
  103. 103. Ahmed SI, Hayat MQ, Tahir M, Mansoor Q, Ismail M, Keck K, et al. Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. BMC Complementary and Alternative Medicine. 2016;16(1):460
  104. 104. Mishra A, Sharma AK, Kumar S, Saxena AK, Pandey AK. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities. BioMed Research International. 2013;2013:915436
  105. 105. Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: An overview. Medicines. 2018;5(3):93
  106. 106. González MBR, Niño VHC. Perspectivas en nutrición humana: Órgano de divulgación academica de la Escuela de Nutrición y Dietética de la Universidad de Antioquia, Perspectivas en Nutrición Humana. Vol. 15. Medellín, Colombia: Universidad de Antioquia, Escuela de Nutrición y Dietética; 2013. pp. 27-40
  107. 107. Ustun O, Senol FS, Kurkcuoglu M, Orhan IE, Kartal M, Baser KHC. Investigation on chemical composition, anticholinesterase and antioxidant activities of extracts and essential oils of Turkish Pinus species and pycnogenol. Industrial Crops and Products. 2012;38:115-123
  108. 108. Zahoor M, Shafiq S, Ullah H, Sadiq A, Ullah F. Isolation of quercetin and mandelic acid from Aesculus indica fruit and their biological activities. BMC Biochemistry. 2018;19(1):5
  109. 109. Cory H, Passarelli S, Szeto J, Tamez M, Mattei J. The role of polyphenols in human health and food systems: A mini-review. Frontiers in Nutrition. 2018;5:87
  110. 110. Andriantsitohaina R, Auger C, Chataigneau T, Étienne-Selloum N, Li H, Martínez MC, et al. Molecular mechanisms of the cardiovascular protective effects of polyphenols. The British Journal of Nutrition. 2012;108(9):1532-1549
  111. 111. Riccioni G. Carotenoids and cardiovascular disease. Current Atherosclerosis Reports. 2009;11(6):434-439
  112. 112. Gammone MA, Riccioni G, D’Orazio N. Carotenoids: Potential allies of cardiovascular health? Food & Nutrition Research. 2015;59:26762
  113. 113. Kavanaugh CJ, Trumbo PR, Ellwood KC. The U.S. Food and Drug Administration’s evidence-based review for qualified health claims: Tomatoes, lycopene, and cancer. Journal of the National Cancer Institute. 2007;99(14):1074-1085
  114. 114. Martí R, Roselló S, Cebolla-Cornejo J. Tomato as a source of carotenoids and polyphenols targeted to cancer prevention. Cancers. 2016;8(6):58
  115. 115. Holzapfel NP, Holzapfel BM, Champ S, Feldthusen J, Clements J, Hutmacher DW. The potential role of lycopene for the prevention and therapy of prostate cancer: From molecular mechanisms to clinical evidence. International Journal of Molecular Sciences. 2013;14(7):14620-14646
  116. 116. Bae J-M, Lee EJ, Guyatt G. Citrus fruit intake and pancreatic cancer risk. Pancreas. 2009;38(2):168-174
  117. 117. Farvid MS, Chen WY, Rosner BA, Tamimi RM, Willett WC, Eliassen AH. Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up. International Journal of Cancer. 2019;144(7):1496-1510
  118. 118. Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. International Journal of Epidemiology. 2017;46(3):1029-1056
  119. 119. Repo-Carrasco-Valencia R, Hellström JK, Pihlava J-M, Mattila PH. Flavonoids and other phenolic compounds in Andean indigenous grains: Quinoa (Chenopodium quinoa), kañiwa (Chenopodium pallidicaule) and kiwicha (Amaranthus caudatus). Food Chemistry. 2010;120(1):128-133
  120. 120. Syama HP, Arya AD, Dhanya R, Nisha P, Sundaresan A, Jacob E, et al. Quantification of phenolics in Syzygium cumini seed and their modulatory role on tertiary butyl-hydrogen peroxide-induced oxidative stress in H9c2 cell lines and key enzymes in cardioprotection. Journal of Food Science and Technology. 2017;54(7):2115-2125
  121. 121. Dludla PV, Joubert E, Muller CJF, Louw J, Johnson R. Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects of rooibos flavonoids and phenylpyruvic acid-2-O-β-D-glucoside. Nutrition & Metabolism (London). 2017;14(1):45
  122. 122. Gao Q, Yang B, Ye Z, Wang J, Bruce IC, Xia Q. Opening the calcium-activated potassium channel participates in the cardioprotective effect of puerarin. European Journal of Pharmacology. 2007;574(2–3):179-184
  123. 123. Han X, Ren D, Fan P, Shen T, Lou H. Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells. European Journal of Pharmacology. 2008;581(1–2):47-53
  124. 124. Sun J, Sun G, Meng X, Wang H, Luo Y, Qin M, et al. Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro. PLoS One. 2013;8(5):e64526
  125. 125. Jarial R, Thakur S, Sakinah M, Zularisam AW, Sharad A, Kanwar SS, et al. Potent anticancer, antioxidant and antibacterial activities of isolated flavonoids from Asplenium nidus. Journal of King Saud University—Science. 2018;30(2):185-192
  126. 126. Dzotam JK, Simo IK, Bitchagno G, Celik I, Sandjo LP, Tane P, et al. In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3′,4′,7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria. BMC Complementary and Alternative Medicine. 2018;18(1):15
  127. 127. Dzoyem JP, Tchamgoue J, Tchouankeu JC, Kouam SF, Choudhary MI, Bakowsky U. Antibacterial activity and cytotoxicity of flavonoids compounds isolated from Pseudarthria hookeri Wight & Arn. (Fabaceae). The South African Journal of Botany. 2018;114:100-103
  128. 128. Geethalakshmi R, Sundaramurthi JC, Sarada DVL. Antibacterial activity of flavonoid isolated from Trianthema decandra against Pseudomonas aeruginosa and molecular docking study of FabZ. Microbial Pathogenesis. 2018;121:87-92
  129. 129. Lim Y-H, Kim I-H, Seo J-J. In vitro activity of kaempferol isolated from the Impatiens balsamina alone and in combination with erythromycin or clindamycin against Propionibacterium acnes. Journal of Microbiology. 2007;45(5):473-477
  130. 130. Hsieh S-K, Xu J-R, Lin N-H, Li Y-C, Chen G-H, Kuo P-C, et al. Antibacterial and laxative activities of strictinin isolated from Pu’er tea (Camellia sinensis). Journal of Food and Drug Analysis. 2016;24(4):722-729
  131. 131. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. Journal of Ethnopharmacology. 2005;100(1–2):72-79
  132. 132. Hashemzaei M, Far AD, Yari A, Heravi RE, Tabrizian K, Taghdisi SM, et al. Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo. Oncology Reports. 2017;38(2):819-828
  133. 133. Nwaeburu CC, Abukiwan A, Zhao Z, Herr I. Quercetin-induced miR-200b-3p regulates the mode of self-renewing divisions in pancreatic cancer. Molecular Cancer. 2017;16(1):23
  134. 134. Adjakly M, Ngollo M, Boiteux J-P, Bignon Y-J, Guy L, Bernard-Gallon D. Genistein and daidzein: Different molecular effects on prostate cancer. Anticancer Research. 2013;33(1):39-44
  135. 135. Abusnina A, Keravis T, Yougbaré I, Bronner C, Lugnier C. Anti-proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1. Molecular Nutrition & Food Research. 2011;55(11):1677-1689
  136. 136. Ide H, Lu Y, Noguchi T, Muto S, Okada H, Kawato S, et al. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer. Cancer Science. 2018;109(4):1230-1238
  137. 137. Ferreres F, Duangsrisai S, Gomes NGM, Suksungworn R, Pereira DM, Gil-Izquierdo A, et al. Anti-inflammatory properties of the stem bark from the herbal drug Vitex peduncularis Wall. ex Schauer and characterization of its polyphenolic profile. Food and Chemical Toxicology. 2017;106(Pt A):8-16
  138. 138. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: An overview. ScientificWorldJournal. 2013;2013:162750
  139. 139. Lu C-L, Zhu Y-F, Hu M-M, Wang D-M, Xu X-J, Lu C-J, et al. Optimization of Astilbin extraction from the rhizome of Smilax glabra, and evaluation of its anti-inflammatory effect and probable underlying mechanism in lipopolysaccharide-induced RAW264.7 macrophages. Molecules. 2015;20(1):625-644
  140. 140. Jing W, Chunhua M, Shumin W. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro. Toxicology and Applied Pharmacology. 2015;285(2):128-135
  141. 141. McKay DL, Blumberg JB. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytotherapy Research. 2006;20(7):519-530
  142. 142. Casagrande R, Georgetti SR, Verri WA, Dorta DJ, dos Santos AC, Fonseca MJV. Protective effect of topical formulations containing quercetin against UVB-induced oxidative stress in hairless mice. Journal of Photochemistry and Photobiology B: Biology. 2006;84(1):21-27
  143. 143. Katiyar SK, Mantena SK, Meeran SM. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism. PLoS One 2011;6(6):e21410
  144. 144. Moore JO, Wang Y, Stebbins WG, Gao D, Zhou X, Phelps R, et al. Photoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis. Carcinogenesis. 2006;27(8):1627-1635
  145. 145. Widyarini S. Protective effect of the isoflavone equol against DNA damage induced by ultraviolet radiation to hairless mouse skin. Journal of Veterinary Science. 2006;7(3):217-223
  146. 146. Squadrito F, Marini H, Bitto A, Altavilla D, Polito F, Adamo EB, et al. Genistein in the metabolic syndrome: Results of a randomized clinical trial. The Journal of Clinical Endocrinology and Metabolism. 2013;98(8):3366-3374
  147. 147. Chen CH, Lin YS, Chien MY, Hou WC, Hu ML. Antioxidant and antihypertensive activities of acteoside and its analogs. Botanical Studies. 2012;53(4):421-429
  148. 148. Bultosa G. Functional foods: Overview. In: Wrigley CW, Corke H, Seetharaman K, Faubion J, editors. Encyclopedia of Food Grains. 2nd edition. London, UK: Academic Press; 2015. pp. 1-10
  149. 149. Esch HL, Kleider C, Scheffler A, Lehmann L. Isoflavones: Toxicological aspects and efficacy. In: Gupta RC, editor. Nutraceuticals: Efficacy, Safety and Toxicity. London, UK: Academic Press; 2016. pp. 465-487
  150. 150. Barnes S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphatic Research and Biology. 2010;8(1):89-98
  151. 151. Malla A, Ramalingam S. Health perspectives of an isoflavonoid genistein and its quantification in economically important plants. In: Grumezescu AM, Holban AM, editors. Role of Materials Science in Food Bioengineering. London, UK: Elsevier; 2018. pp. 353-379
  152. 152. Hilakivi-Clarke L, Andrade JE, Helferich W. Is soy consumption good or bad for the breast? The Journal of Nutrition. 2010;140(12):2326S-2334S
  153. 153. Watanabe S, Uehara M. Health effects and safety of soy and isoflavones. In: The Role of Functional Food Security in Global Health. Elsevier; 2019. pp. 379-394
  154. 154. Kimura T. East meets west: Ethnic differences in prostate cancer epidemiology between east Asians and Caucasians. Chinese Journal of Cancer. 2012;31(9):421-429
  155. 155. Uifălean A, Schneider S, Gierok P, Ionescu C, Iuga C, Lalk M. The impact of soy isoflavones on MCF-7 and MDA-MB-231 breast cancer cells using a global metabolomic approach. International Journal of Molecular Sciences. 2016;17(9):1443
  156. 156. Theil C, Briese V, Gerber B, Richter D-U. The effects of different lignans and isoflavones, tested as aglycones and glycosides, on hormone receptor-positive and -negative breast carcinoma cells in vitro. Archives of Gynecology and Obstetrics. 2011;284(2):459-465
  157. 157. Uifălean A, Schneider S, Ionescu C, Lalk M, Iuga C. Soy isoflavones and breast cancer cell lines: Molecular mechanisms and future perspectives. Molecules. 2015;21(1):13
  158. 158. Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Research. 2001;61(13):5045-5050
  159. 159. Ju YH, Allred KF, Allred CD, Helferich WG. Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations. Carcinogenesis. 2006;27(6):1292-1299
  160. 160. Setchell KDR, Brown NM, Zhao X, Lindley SL, Heubi JE, King EC, et al. Soy isoflavone phase II metabolism differs between rodents and humans: Implications for the effect on breast cancer risk. The American Journal of Clinical Nutrition. 2011;94(5):1284-1294
  161. 161. Messina M. Impact of soy foods on the development of breast cancer and the prognosis of breast cancer patients. Complementary Medicine Research. 2016;23(2):75-80
  162. 162. American Cancer Society. Soy and Cancer Risk: Our Expert’s Advice. 2019. Available from: https://www.cancer.org/latest-news/soy-and-cancer-risk-our-experts-advice.html [Accessed: 09 February 2020]
  163. 163. American Institute for Cancer Research (AICR). Foods that fight cancer. Soy. Available from: https://www.aicr.org/cancer-prevention/food-facts/soy/#research [Accessed: 09 February 2020]
  164. 164. Ramdath DD, Padhi EM, Sarfaraz S, Renwick S, Duncan AM. Beyond the cholesterol-lowering effect of soy protein: A review of the effects of dietary soy and its constituents on risk factors for cardiovascular disease. Nutrients. 2017;9(4):324
  165. 165. Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: A quality assessment and meta-analysis of randomized, controlled studies. Journal of the American College of Nutrition. 2011;30(2):79-91
  166. 166. Sathyapalan T, Aye M, Rigby AS, Thatcher NJ, Dargham SR, Kilpatrick ES, et al. Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause. Nutrition, Metabolism and Cardiovascular Diseases. 2018;28(7):691-697
  167. 167. Martin D, Song J, Mark C, Eyster K. Understanding the cardiovascular actions of soy Isoflavones: Potential novel targets for antihypertensive drug development. Cardiovascular & Hematological Disorders-Drug Targets. 2008;8(4):297-312
  168. 168. Food and Drug Administration.: Code of Federal Regulations Title 21.101.82 Health Claims: Soy Protein and Risk of Coronary Heart Disease (CHD). Revised as of April 1, 2018
  169. 169. Jenkins DJA, Blanco Mejia S, Chiavaroli L, Viguiliouk E, Li SS, Kendall CWC, et al. Cumulative meta-analysis of the soy effect over time. Journal of the American Heart Association. 2019;8(13):e012458
  170. 170. Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: Mechanisms underlying its effects on pancreatic β-cell function. Food & Function. 2013;4(2):200-212
  171. 171. Li W, Ruan W, Peng Y, Wang D. Soy and the risk of type 2 diabetes mellitus: A systematic review and meta-analysis of observational studies. Diabetes Research and Clinical Practice. 2018;137:190-199
  172. 172. Goodman-Gruen D, Kritz-Silverstein D. Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. The Journal of Nutrition. 2001;131(4):1202-1206
  173. 173. Konishi K, Wada K, Yamakawa M, Goto Y, Mizuta F, Koda S, et al. Dietary soy intake is inversely associated with risk of type 2 diabetes in Japanese women but not in men. The Journal of Nutrition. 2019;149(7):1208-1214
  174. 174. Li R, Zhang Y, Rasool S, Geetha T, Babu JR. Effects and underlying mechanisms of bioactive compounds on type 2 diabetes mellitus and Alzheimer’s disease. Oxidative Medicine and Cellular Longevity. 2019;2019:1-25
  175. 175. Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KH, MacLeod J, et al. Nutrition therapy for adults with diabetes or prediabetes: A consensus report. Diabetes Care. 2019;42(5):731-754
  176. 176. Zheng X, Lee S-K, Chun OK. Soy Isoflavones and osteoporotic bone loss: A review with an emphasis on modulation of bone remodeling. Journal of Medicinal Food. 2016;19(1):1-14
  177. 177. Filipović B, Šošić-Jurjević B, Ajdžanović V, Živanović J, Manojlović-Stojanoski M, Nestorović N, et al. The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis. Journal of Anatomy. 2018;233(2):204-212
  178. 178. Arcoraci V, Atteritano M, Squadrito F, D’anna R, Marini H, Santoro D, et al. Antiosteoporotic activity of genistein aglycone in postmenopausal women: Evidence from a post-hoc analysis of a multicenter randomized controlled trial. Nutrients. 2017;9:179
  179. 179. National Center for Complementary and Integrative Health. Soy. Available from: https://nccih.nih.gov/health/soy/ataglance.htm#know [Accessed: 09 February 2020]
  180. 180. Franco OH, Chowdhury R, Troup J, Voortman T, Kunutsor S, Kavousi M, et al. Use of plant-based therapies and menopausal symptoms. Journal of the American Medical Association. 2016;315(23):2554
  181. 181. Dunneram Y, Chung HF, Cade JE, Greenwood DC, Dobson AJ, Mitchell ES, et al. Soy intake and vasomotor menopausal symptoms among midlife women: A pooled analysis of five studies from the InterLACE consortium. European Journal of Clinical Nutrition. 2019;3(11):1501-1511
  182. 182. Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database of Systematic Reviews. 2013;(12)
  183. 183. Barnes S, Gold EB, Basaria SS, Aso T, Kronenberg F, Frankenfeld CL, et al. The role of soy isoflavones in menopausal health: Report of the North American Menopause Society/Wulf H. Utian translational science symposium in Chicago, IL (October 2010). Menopause: The Journal of The North American Menopause Society. 2011;18(7):732-753
  184. 184. van Dam JEG, van den Broek LAM, Boeriu CG. Polysaccharides in human health care. Natural Product Communications. 2017;12(6):821-830
  185. 185. Pop OL, Salanță LC, Pop CR, Coldea T, Socaci SA, Suharoschi R, et al. Prebiotics and dairy applications. In: Galanakis CM, editor. Dietary Fiber: Properties, Recovery, and Applications. London, UK: Academic Press; 2019. pp. 247-277
  186. 186. Zhang T, Yang Y, Liang Y, Jiao X, Zhao C. Beneficial effect of intestinal fermentation of natural polysaccharides. Nutrients. 2018;10(8):1055
  187. 187. Persin Z, Stana-Kleinschek K, Foster TJ, van Dam JEG, Boeriu CG, Navard P. Challenges and opportunities in polysaccharides research and technology: The EPNOE views for the next decade in the areas of materials, food and health care. Carbohydrate Polymers. 2011;84(1):22-32
  188. 188. Liu J, Willför S, Xu C. A review of bioactive plant polysaccharides: Biological activities, functionalization, and biomedical applications. Bioactive Carbohydrates and Dietary Fibre. 2015;5(1):31-61
  189. 189. Lovegrove A, Edwards CH, De Noni I, Patel H, El SN, Grassby T, et al. Role of polysaccharides in food, digestion, and health. Critical Reviews in Food Science and Nutrition. 2017;57(2):237-253
  190. 190. Nie Y, Lin Q, Luo F. Effects of non-starch polysaccharides on inflammatory bowel disease. International Journal of Molecular Sciences. 2017;18(7):1372
  191. 191. Lattimer JM, Haub MD. Effects of dietary fiber and its components on metabolic health. Nutrients. 2010;2(12):1266-1289
  192. 192. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced inflammatory bowel disease models in rodents. The Korean Journal of Physiology & Pharmacology. 2014;18(4):279-288
  193. 193. Huang X, Nie S, Xie M. Interaction between gut immunity and polysaccharides. Critical Reviews in Food Science and Nutrition. 2017;57(14):2943-2955
  194. 194. De Silva DD, Rapior S, Fons F, Bahkali AH, Hyde KD. Medicinal mushrooms in supportive cancer therapies: An approach to anti-cancer effects and putative mechanisms of action. Fungal Diversity. 2012;55(1):1-35
  195. 195. Ren L, Perera C, Hemar Y. Antitumor activity of mushroom polysaccharides: A review. Food & Function. 2012;3(11):1118
  196. 196. Jin M, Huang Q, Zhao K, Shang P. Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L. International Journal of Biological Macromolecules. 2013;54:16-23
  197. 197. Collins HM, Burton RA, Topping DL, Liao ML, Bacic A, Fincher GB. Variability in fine structures of noncellulosic cell wall polysaccharides from cereal grains: Potential importance in human health and nutrition. Cereal Chemistry. 2010;87(4):272-282
  198. 198. van Dam JEG, van den Broek LAM, Boeriu CG. Polysaccharides in human health care. Natural Product Communications. 2017;12(6). DOI: 10.1177/1934578X1701200604
  199. 199. Koivula A, Voutilainen S, Pere J, Kruus K, Suurnäkki A, van den Broek LAM, et al. Polysaccharide-acting enzymes and their applications. In: The European Polysaccharide Network of Excellence (EPNOE). Vienna: Springer; 2012. pp. 375-392
  200. 200. Lu X, Li N, Qiao X, Qiu Z, Liu P. Effects of thermal treatment on polysaccharide degradation during black garlic processing. LWT—Food Science and Technology. 2018;95:223-229
  201. 201. Woo KS, Kim HY, Hwang IG, Lee SH, Jeong HS. Characteristics of the thermal degradation of glucose and maltose solutions. Preventive Nutrition and Food Science. 2015;20(2):102-109
  202. 202. Taghizadeh MT, Abdollahi R. A kinetics study on the thermal degradation of starch/poly (vinyl alcohol) blend. Chemical and Materials Engineering. 2015;3(4):73-78
  203. 203. Faure AM, Knüsel R, Nyström L. Effect of the temperature on the degradation of β-glucan promoted by iron(II). Bioactive Carbohydrates and Dietary Fibre. 2013;2(2):99-107
  204. 204. Golon A, González FJ, Dávalos JZ, Kuhnert N. Investigating the thermal decomposition of starch and cellulose in model systems and toasted bread using domino tandem mass spectrometry. Journal of Agricultural and Food Chemistry. 2013;61(3):674-684
  205. 205. Li S, Xiong Q, Lai X, Li X, Wan M, Zhang J, et al. Molecular modification of polysaccharides and resulting bioactivities. Comprehensive Reviews in Food Science and Food Safety. 2016;15(2):237-250
  206. 206. Bhosale RR, Gangadharappa HV, Moin A, Gowda DV, Ali R, Osmani A. A review on grafting modification of polysaccharides by microwave irradiation-distinctive practice for application in drug delivery. International Journal of Current Pharmaceutical Review and Research. 2015;6(1):8-17
  207. 207. Łukasiewicz M, Kowalski G, Ptaszek A. Microwave-synthesized polysaccharide copolymers. In: Polysaccharides. Cham: Springer International Publishing; 2014. pp. 1-35
  208. 208. Goh KKT, Kumar R, Wong S-S. Functionality of non-starch polysaccharides (NSPs). In: Functional Foods and Dietary Supplements. Chichester, UK: John Wiley & Sons, Ltd; 2014. pp. 187-225
  209. 209. Villay A, Lakkis de Filippis F, Picton L, Le Cerf D, Vial C, Michaud P. Comparison of polysaccharide degradations by dynamic high-pressure homogenization. Food Hydrocolloids. 2012;27(2):278-286
  210. 210. Yang B, Jiang Y, Wang R, Zhao M, Sun J. Ultra-high pressure treatment effects on polysaccharides and lignins of longan fruit pericarp. Food Chemistry. 2009;112(2):428-431
  211. 211. Sabharwal S, Varshney L, Chaudhari AD, Rammani SP. Radiation processing of natural polymers: Achievements & trends. In: Radiation Processing of polysaccharides. Vienna, Austria: International Atomic Energy Agency; 2004. pp. 29-38
  212. 212. Ponomarev A, Ershov B. Radiation-induced high-temperature conversion of cellulose. Molecules. 2014;19(10):16877-16908
  213. 213. Byun E-H, Kim J-H, Sung N-Y, Choi J, Lim S-T, Kim K-H, et al. Effects of gamma irradiation on the physical and structural properties of β-glucan. Radiation Physics and Chemistry. 2008;77(6):781-786
  214. 214. Cieśla KA. Radiation modification of polysaccharides and their composites/nanocomposites. In: Sun Y, Chmielewski AG, editors. Applications of Ionizing Radiation in Materials Processing. Volume 2. Poland, Warszawa: Institute of Nuclear Chemistry and Technology; 2017. pp. 327-354
  215. 215. Usydus Z, Szlinder-Richert J. Functional properties of fish and fish products: A review. International Journal of Food Properties. 2012;15(4):823-846
  216. 216. Gormley R, Holm F. Functional Foods: Some Pointers for Success. Dublin, Ireland: UCD Institute of Food and Health; 2010. Available from: https://www.ucd.ie/t4cms/ffnet%20funct%20fds%20final%20e-publication%20jan%202011.pdf [Accessed: 09 February 2020]
  217. 217. Ananey-Obiri D, Tahergorabi R. Development and characterization of fish-based superfoods. In: Current Topics on Superfoods. Rijeca: InTech; 2018
  218. 218. Naqash SY, Nazeer RA. Antioxidant activity of hydrolysates and peptide fractions of Nemipterus japonicus and Exocoetus volitans muscle. Journal of Aquatic Food Product Technology. 2010;19(3–4):180-192
  219. 219. Jumeri KSM. Antioxidant and anticancer activities of enzymatic hydrolysates of solitary tunicate (Styela clava). Food Science and Biotechnology. 2011;20(4):1075-1085
  220. 220. Shahidi F. Omega-3 fatty acids and marine oils in cardiovascular and general health: A critical overview of controversies and realities. Journal of Functional Foods. 2015;19:797-800
  221. 221. Jimeno J, Faircloth G, Sousa-Faro J, Scheuer P, Rinehart K. New marine derived anticancer therapeutics—A journey from the sea to clinical trials. Marine Drugs. 2004;2(1):14-29
  222. 222. Simmons TL, Andrianasolo E, McPhail K, Flatt P, Gerwick WH. Marine natural products as anticancer drugs. Molecular Cancer Therapeutics. 2005;4(2):333-342
  223. 223. Wilson-Sanchez G, Moreno-Félix C, Velazquez C, Plascencia-Jatomea M, Acosta A, Machi-Lara L, et al. Antimutagenicity and antiproliferative studies of Lipidic extracts from White Shrimp (Litopenaeus vannamei). Marine Drugs. 2010;8(11):2795-2809
  224. 224. Suarez-Jimenez G-M, Burgos-Hernandez A, Ezquerra-Brauer J-M. Bioactive peptides and depsipeptides with anticancer potential: Sources from marine animals. Marine Drugs. 2012;10(5):963-986
  225. 225. Kim S-K, Wijesekara I. Development and biological activities of marine-derived bioactive peptides: A review. Journal of Functional Foods. 2010;2(1):1-9
  226. 226. Ryan JT, Ross RP, Bolton D, Fitzgerald GF, Stanton C. Bioactive peptides from muscle sources: Meat and fish. Nutrients. 2011;3(9):765-791
  227. 227. Alasalvar C, Taylor T, editors. Seafoods—Quality, Technology and Nutraceutical Applications. Berlin, Heidelberg: Springer; 2002
  228. 228. Slizyte R, Rommi K, Mozuraityte R, Eck P, Five K, Rustad T. Bioactivities of fish protein hydrolysates from defatted salmon backbones. Biotechnology Reports. 2016;11:99-109
  229. 229. Hamada Y, Shioiri T. Recent progress of the synthetic studies of biologically active marine cyclic peptides and depsipeptides. Chemical Reviews. 2005;105(12):4441-4482
  230. 230. Aneiros A, Garateix A. Bioactive peptides from marine sources: Pharmacological properties and isolation procedures. Journal of Chromatography B. 2004;803(1):41-53
  231. 231. Zampella A, Sepe V, Luciano P, Bellotta F, Monti MC, D’Auria MV, et al. Homophymine A, an anti-HIV Cyclodepsipeptide from the sponge Homophymia sp. The Journal of Organic Chemistry. 2008;73(14):5319-5327
  232. 232. Blunt JW, Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Natural Product Reports. 2018;35(1):8-53
  233. 233. Wesson KJ, Hamann MT. Keenamide A. A bioactive cyclic peptide from the marine mollusk Pleurobranchus forskalii. Journal of Natural Products. 1996;59(6):629-631
  234. 234. Carroll A, Bowden B, Coll J, Hockless D, Skelton B, White A. Studies of Australian ascidians. IV. Mollamide, a cytotoxic cyclic Heptapeptide from the compound ascidian Didemnum molle. Australian Journal of Chemistry. 1994;47(1):61
  235. 235. Friess W. Collagen--biomaterial for drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. 1998;45(2):113-136
  236. 236. Li W-L, Yi Y-H, Wu H-M, Xu Q-Z, Tang H-F, Zhou D-Z, et al. Isolation and structure of the cytotoxic cycloheptapeptide, phakellistatin 13. Journal of Natural Products. 2003;66(1):146-148
  237. 237. Nakazawa H, Kitano K, Cioca DP, Ishikawa M, Ueno M, Ishida F, et al. Induction of polyploidization by jaspamide in HL-60 cells. Acta Haematologica. 2000;104(2–3):65-71
  238. 238. Rustad T, Storrø I, Slizyte R. Possibilities for the utilisation of marine by-products. International Journal of Food Science and Technology. 2011;46(10):2001-2014
  239. 239. Hsu K-C, Li-Chan ECY, Jao C-L. Antiproliferative activity of peptides prepared from enzymatic hydrolysates of tuna dark muscle on human breast cancer cell line MCF-7. Food Chemistry. 2011;126(2):617-622
  240. 240. Barrow C, Shahidi F, editors. Marine Nutraceuticals and Functional Foods. Florida, USA: CRC Press; 2007
  241. 241. Hayes M, Flower D. Bioactive peptides from marine processing byproducts. In: Bioactive Compounds from Marine Foods. Chichester, UK: John Wiley & Sons Ltd; 2013. pp. 57-71
  242. 242. Undeland I, Lindqvist H, Chen-Yun Y, Falch E, Ramel A, Cooper M, et al. Seafood and health: What is the full story? In: Luten, JB, editor. Marine Functional Food. Wageningen, The Netherlands: Wageningen Academic Press; 2009. pp. 17-87
  243. 243. Bae I, Osatomi K, Yoshida A, Osako K, Yamaguchi A, Hara K. Biochemical properties of acid-soluble collagens extracted from the skins of underutilised fishes. Food Chemistry. 2008;108(1):49-54
  244. 244. Matmaroh K, Benjakul S, Prodpran T, Encarnacion AB, Kishimura H. Characteristics of acid soluble collagen and pepsin soluble collagen from scale of spotted golden goatfish (Parupeneus heptacanthus). Food Chemistry. 2011;129(3):1179-1186
  245. 245. Liu D, Liang L, Regenstein JM, Zhou P. Extraction and characterisation of pepsin-solubilised collagen from fins, scales, skins, bones and swim bladders of bighead carp (Hypophthalmichthys nobilis). Food Chemistry. 2012;133(4):1441-1448
  246. 246. Gómez-Guillén MC, Giménez B, López-Caballero ME, Montero MP. Functional and bioactive properties of collagen and gelatin from alternative sources: A review. Food Hydrocolloids. 2011;25(8):1813-1827
  247. 247. Yai H. Edible films and coatings: Characteristics and properties. International Food Research Journal. 2008;15(3):237-248
  248. 248. Zhang M, Liu W, Li G. Isolation and characterisation of collagens from the skin of largefin longbarbel catfish (Mystus macropterus). Food Chemistry. 2009;115(3):826-831
  249. 249. Santos MH, Silva RM, Dumont VC, Neves JS, Mansur HS, Heneine LGD. Extraction and characterization of highly purified collagen from bovine pericardium for potential bioengineering applications. Materials Science and Engineering: C. 2013;33(2):790-800
  250. 250. Ciarlo AS, Paredi ME, Fraga AN. Isolation of soluble collagen from hake skin (Merluccius hubbsi). Journal of Aquatic Food Product Technology. 1997;6(1):65-77
  251. 251. Nagai T, Araki Y, Suzuki N. Collagen of the skin of ocellate puffer fish (Takifugu rubripes). Food Chemistry. 2002;78(2):173-177
  252. 252. Wang S, Hou H, Hou J, Tao Y, Lu Y, Yang X, et al. Characterization of acid-soluble collagen from bone of Pacific cod (Gadus macrocephalus ). Journal of Aquatic Food Product Technology. 2013;22(4):407-420
  253. 253. Skierka E, Sadowska M. The influence of different acids and pepsin on the extractability of collagen from the skin of Baltic cod (Gadus morhua). Food Chemistry. 2007;105(3):1302-1306
  254. 254. Uriarte-Montoya MH, Arias-Moscoso JL, Plascencia-Jatomea M, Santacruz-Ortega H, Rouzaud-Sández O, Cardenas-Lopez JL, et al. Jumbo squid (Dosidicus gigas) mantle collagen: Extraction, characterization, and potential application in the preparation of chitosan–collagen biofilms. Bioresource Technology. 2010;101(11):4212-4219
  255. 255. Bakar J, Razali UH, Hashim DM, Sazili AQ, Kaur H, Rahman RA, et al., inventors; Universiti Putra Malaysia (UPM), assignee. Collagen extraction from aquatic animals. United States patent application US20140147400A1. 2012
  256. 256. Tabarestani HS, Maghsoudlou Y, Motamedzadegan A, Mahoonak AR, Rostamzad H. Study on some properties of acid-soluble collagens isolated from fish skin and bones of rainbow trout (Onchorhynchus mykiss). International Food Research Journal. 2012;19(1):251-257
  257. 257. Hema GS, Shyni K, Suseela M, Anandan R, George N, Lakshmanan PT. A simple method for isolation of fish skin collagen-biochemical characterization of skin collagen extracted from Albacore tuna (Thunnus alalunga), dog shark (Scoliodon sorrakowah), and Rohu (Labeo rohita). Annals of Biological Research. 2013;4(1):271-278
  258. 258. Alfaro AT, Biluca FC, Marquetti C, Tonial IB, de Souza NE. African catfish (Clarias gariepinus) skin gelatin: Extraction optimization and physical–chemical properties. Food Research International. 2014;65:416-422
  259. 259. Fan H, Dumont M-J, Simpson BK. Extraction of gelatin from salmon (Salmo salar) fish skin using trypsin-aided process: Optimization by Plackett–Burman and response surface methodological approaches. Journal of Food Science and Technology. 2017;54(12):4000-4008
  260. 260. Tan Y, Chang SKC. Isolation and characterization of collagen extracted from channel catfish (Ictalurus punctatus) skin. Food Chemistry. 2018;242:147-155
  261. 261. Tanaka T, Takahashi K, Tsubaki K, Hirata M, Yamamoto K, Biswas A, et al. Isolation and characterization of acid-soluble bluefin tuna (Thunnus orientalis) skin collagen. Fisheries and Aquatic Science. 2018;21(1):7
  262. 262. Surette ME. The science behind dietary omega-3 fatty acids. Canadian Medical Association Journal. 2008;178(2):177-180
  263. 263. Whelan J, Rust C. Innovative dietary sources of N-3 fatty acids. Annual Review of Nutrition. 2006;26(1):75-103
  264. 264. Jónasdóttir S. Fatty acid profiles and production in marine phytoplankton. Marine Drugs. 2019;17(3):151
  265. 265. Greenberg P. The Omega Principle: Seafood and The Quest for a Long Life and a Healthier Planet. London, UK: Penguin Press; 2018
  266. 266. Pike IH, Jackson A. Fish oil: Production and use now and in the future. Lipid Technology. 2010;22(3):59-61
  267. 267. Russo GL. Dietary n−6 and n−3 polyunsaturated fatty acids: From biochemistry to clinical implications in cardiovascular prevention. Biochemical Pharmacology. 2009;77(6):937-946
  268. 268. Calder PC. Mechanisms of action of (n-3) fatty acids. The Journal of Nutrition. 2012;142(3):592S-599S
  269. 269. Maehre HK, Jensen I-J, Elvevoll EO, Eilertsen K-E. ω-3 fatty acids and cardiovascular diseases: Effects, mechanisms and dietary relevance. International Journal of Molecular Sciences. 2015;16(9):22636-22661
  270. 270. Torres N, Guevara-Cruz M, Velázquez-Villegas LA, Tovar AR. Nutrition and atherosclerosis. Archives of Medical Research. 2015;46(5):408-426
  271. 271. Bjerregaard P. Disease pattern in Greenland: Studies on morbidity in Upernavik 1979-1980 and mortality in Greenland 1968–1985. Arctic Medical Research. 1991;50(Suppl 4):1-62
  272. 272. Kromhout D, Bosschieter EB, Coulander CDL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. The New England Journal of Medicine. 1985;312(19):1205-1209
  273. 273. Calder P, Grimble R. Polyunsaturated fatty acids, inflammation and immunity. European Journal of Clinical Nutrition. 2002;56(S3):S14-S19
  274. 274. Calvo MJ, Martínez MS, Torres W, Chávez-Castillo M, Luzardo E, Villasmil N, et al. Omega-3 polyunsaturated fatty acids and cardiovascular health: A molecular view into structure and function. Vessel Plus. 2017;1(3):116-128
  275. 275. Shaikh SR. Biophysical and biochemical mechanisms by which dietary N-3 polyunsaturated fatty acids from fish oil disrupt membrane lipid rafts. The Journal of Nutritional Biochemistry. 2012;23(2):101-105
  276. 276. Ferreri C, Masi A, Sansone A, Giacometti G, Larocca A, Menounou G, et al. Fatty acids in membranes as homeostatic, metabolic and nutritional biomarkers: Recent advancements in analytics and diagnostics. Diagnostics. 2016;7(1):1
  277. 277. Hussein JS. Cell membrane fatty acids and health. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(Suppl 3):38-46
  278. 278. Hashimoto M, Hossain MS, Yamasaki H, Yazawa K, Masumura S. Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids. 1999;34(12):1297-1304
  279. 279. Krebs JD, Browning LM, McLean NK, Rothwell JL, Mishra GD, Moore CS, et al. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. International Journal of Obesity. 2006;30(10):1535-1544
  280. 280. Buckley JD, Howe PRC. Long-chain Omega-3 polyunsaturated fatty acids may Be beneficial for reducing obesity—A review. Nutrients. 2010;2(12):1212-1230
  281. 281. Ryan KK, Li B, Grayson BE, Matter EK, Woods SC, Seeley RJ. A role for central nervous system PPAR-γ in the regulation of energy balance. Nature Medicine. 2011;17(5):623-626
  282. 282. Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G, et al. Brain PPAR-γ promotes obesity and is required for the insulin–sensitizing effect of thiazolidinediones. Nature Medicine. 2011;17(5):618-622
  283. 283. Ismail A, Bannenberg G, Rice HB, Schutt E, MacKay D. Oxidation in EPA- and DHA-rich oils: An overview. Lipid Technology. 2016;28(3–4):55-59
  284. 284. Mozuraityte R, Kristinova V, Rustad T, Storrø I. The role of iron in peroxidation of PUFA: Effect of pH and chelators. European Journal of Lipid Science and Technology. 2016;118(4):658-668
  285. 285. Bannenberg G, Mallon C, Edwards H, Yeadon D, Yan K, Johnson H, et al. Omega-3 long-chain polyunsaturated fatty acid content and oxidation state of fish oil supplements in New Zealand. Scientific Reports. 2017;7(1):1488
  286. 286. Schaich KM. Lipid oxidation: Theoretical aspects. In: Bailey’s Industrial Oil and Fat Products. Hoboken, NJ, USA: John Wiley & Sons Inc.; 2005
  287. 287. Cropotova J, Mozuraityte R, Standal IB, Rustad T. Assessment of lipid oxidation in Atlantic mackerel (Scomber scombrus) subjected to different antioxidant and sous-vide cooking treatments by conventional and fluorescence microscopy methods. Food Control. 2019;104:1-8
  288. 288. GOED Omega-3|Global Organization for EPA and DHA Omega-3 [Internet]. Available from: https://goedomega3.com/index.php. [Accessed: 26 August 2019]

Written By

Liana Claudia Salanță, Alina Uifălean, Cristina-Adela Iuga, Maria Tofană, Janna Cropotova, Oana Lelia Pop, Carmen Rodica Pop, Mihaela Ancuța Rotar, Mirandeli Bautista-Ávila and Claudia Velázquez González

Submitted: September 12th, 2019 Reviewed: January 16th, 2020 Published: February 18th, 2020