Mulberry

Abstract

Mulberry plant belongs to the family Moracea from the genus Morus and can be cultivated in mountains, plains, and valleys, even in humid and rain-fed areas. Many various varieties of this plant are present around the world, but three prime varieties include, that is, native red mulberry (Morus rubra), East Asian white mulberry (Morus alba), and southwestern Asian black mulberry (Morus nigra). The presence of certain biologically active compounds in its fruit provides several pharmacological benefits to health. Polyphenols, flavonols, anthocyanin, flavonoids, anthocyanins, benzoic acid, and hydroxycinnamic acid are the major bioactive active compounds responsible for pharmacological benefits, that is, anticholesterol, antidiabetic, antioxidative, and antiobesity effects fruit of this plant can be consumed as whole fruit, as juice, and as spread but its preservation is difficult due to its high water content. Therefore, this chapter will aim to focus on different types of mulberry plants and the pharmacologic benefits of different mulberry fruits.

1. Introduction

The family Moraceae shelters mulberry (Morus), an East Asian plant; throughout the world, this plant is widely spread in various biological and geographic zones by farming in tropical, subtropical, and temperate climates and by natural occurrence in forestry [1]. The word “mulberry” has a stimulating etymological progression; the German word for berry, beri, was combined with the Latin word Morus to create the word múlbere, múlbere was then transformed into the German name Maulbeer, afterward which was then morphed into the Dutch word moerbezie, and ultimately was transformed to mulberry an English word [2]. Its origin is in Asia, grows in length to about 16 m, an ecologically important plant as its leaves are used as feed for silkworms and this plant is wind cross-fertilized and also set fruit without pollination [3]. Depending on the plant’s age and cultivars, mulberry fruit contains a wide diversity of nutritive and bioactive compounds, that is, amino acids, fatty acids, vitamins, minerals, rutin, quercetin, anthocyanins, chlorogenic acid, and polysaccharides. Due to the presence of these compounds in its fruit, it possesses antioxidative, neuroprotective, antiatherosclerotic, immunomodulative, antitumor, antihyperglycemic, and hypolipidemic properties [4] among berries; mulberries are richest in phenolics and anthocyanins [5]. Mulberry fruits are categorized as functional foods owing to the occurrence of these bioactive chemicals and the provision of medicinal properties important for human health [6]. Although this fruit is native to Asia but has been broadly spread to Europe, Asia, North America, Africa, Latin America, and South America [7]. Three main types of this plant include white mulberry (M. alba) originated in Western Asia, red mulberry (Morus rubra) originated in North and South America and black mulberry (Morus nigra) originated from Southern Russia [8]. The Mulberry plant offers multibenefits, that is, food, fodder, and fuel; its fruit is eaten as a raw fruit as fruit juice as fruit puree, and also used in sericulture [9] used as molasses, vinegar, and jam [10]. Communities in southeast region consume dried mulberries as an appetizer. They process mulberry in its juice and then combine the juice with starch afterward, boiling and drying under the sun, forming pestil; they also mix mulberry fruit juice with starch and walnut kernel, forming a solid sausage shape and lastly, drying under the sun forming kome [11] thus providing substantial marketing value due to the nutritious and distinct characteristics [10]. It has been affirmed that mulberry fruits and their products, such as molasses, juices, compotes, and jams, could aid in the management of some coronary, gastric, and intestinal problems [12]. Agrarians in China and India cultivate mulberry plants for silkworms, and European cultivate mulberry plants for their fruit [13]. With respect to fruit production, there are three prime varieties of mulberries, that is, M. alba, Morus rubra, and Morus nigra.

2. Major types of mulberry fruit

2.1 White mulberry (M. alba)

M. alba plant is also known as Tutam in Sanskrit, Tut in Hindi, Mulberry in English, Malbari in Malayalam, and Musukette in Tamil. This plant is moderately sized, three to six meters tall, and categorized as a shrub or tree. In Chinese medicine, M. alba plant provides a long list of medicinal benefits and traditionally its fruit is traditionally used to nourish blood, treat anemia, fatigue, and prevent premature graying of hair. Besides its fruit, all its parts offer medicinal benefits in treating asthma, edema, cough, bronchitis, insomnia, influenza, diabetes, eye infections, and nose bleeding. The indigeneous system has providediuretic, laxative, antibacterial, and anthelmintic properties [14].

2.2 Red mulberry (M. rubra)

Morus is a Latin word for mulberry, and rubra is a Latin word for red. Trees of this plant are found in damp soils, floodplains, and moist sites in South Florida, West Texas, Minnesota, Ontario, and mid-Atlantic regions. In different areas, different parts of this plant are used to treat diseases, that is, Albama and Indians are using its root to treat urinary tract issues, its juice is being used by Rappahannock community to treat ringworm by rubbing over the skin, Cherokee uses its bark to eliminate intestinal worms by steeping its bark and ingesting the liquid lastly, its root bark is used in Meskwaki to treat many ailments [2].

2.3 Black mulberry (M. nigra)

M. nigra is a species of plant in the family Moraceae, innate in humid, subtropical, and pleasant zones in Asia, Europe, North America, South America, and Africa [13]. This is one of the very important specie of Morus genus, its sensory evaluation indicates that it has sweet, sour, musky and woody flavors and has woody, fresh aroma physiognomies [15], dark black color of the fruit due to the presence of anthocyanins [16]. This plant is grown in many countries without any particular protection, and fortunately, its barks, leaves, and berries all provide medicinal properties, that is, berries for treating inflammation and blood bleeding, bark for treating toothache, and leaves are used as an antidote. Fortunately, its trees are super resistant to pests and other diseases, due to which its fruit can make products with good nutritional value leading to healthy, organic, and ecological lifestyle [17]. In Europe, leaves of M. nigra have been used to stimulate the production of insulin production in people with diabetes mellitus [18]. In Turkey, M. nigra has been used in folk medicine to treat fever, to buffer the liver, to support joints, to manage blood pressure, and to assist the passage of urine [19].

3. Nutritional composition of mulberry fruit

Mulberry fruit, when ripened, offers great taste, aroma, and flavor. It is valued to consume it as raw fruit rather than consuming it in its processed form [20]. The nutritional composition of fruits is dependent on the ripeness, type of soil, season, variants in genotypes, and postharvest observations. Taste, color, and browning of the fruit are dependent on the concentration of phenolics compounds [21]. Mulberry fruits contain good water content, that is, >70%, are low in calories, and are rich in nutrients and antioxidants; they have great composition to maintain a healthy body status [22]. Mulberries are an excellent combination of polyphenols, that is, flavones, isoflavanols, lignans, tannins, anthocyanins, catechins, and flavonols. The popularity of this fruit in the human fruit is basically due to the presence of these phytochemicals [23].

Mulberries grown in the Xinjiang region of China have high potassium content, followed by calcium and magnesium, the high iron content of black mulberry from China has made them a valuable source for overcoming iron deficiencies. A high percentage of linoleic acid, that is, 52.3% present in white mulberry obtained from Xinjiang, China [24]. 4.2 mg/100 g iron is present in M. alba and nigra, Russian mulberry and black mulberry obtained from China have high iron content ranging from 11.4 to 11.9 mg/100 g FW, and the bioavailability of iron can be enhanced by vitamin C’s chelating properties; the highest value of vitamin C is present in M. alba (22.4 mg/100 ml) followed by M. nigra (21.8 mg/100 ml) and then M. rubra (19.4 mg/100 ml) [22]. In context to the fatty acid composition of mulberry fruits, linoleic acid is the most dominant one, followed by palmitic and oleic acid [22]. Mulberry fruits obtained from southeastern Spain contain a good percentage of protein and are considered as a high protein source; M. alba has high protein content than M. nigra [25].

3.1 Major phytochemicals

Anthocyanins: A flavonoid and a major contributor to the color of flower and fruit ranging from red to blue and purple, gained great importance due to its biological benefits, that is, antitumor, antidiabetic, and antioxidant properties. Mulberry fruit contains many various types of anthocyanins, that is, cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), pelargonidin-3-glucoside, pelargonidin-3-rutinoside, cyanidin 3-O-(6“-O-α-rhamnopyranosyl-β-D-glucopyranoside), cyanidin 3-O-(6”-O-α-rhamnopyranosyl-β-D-galactopyranoside), cyanidin 3-O-β-D-galactopyranoside, cyanidin 7-O-β-D-glucopyranoside, and petunidin 3-O-β-glucopyranoside. Among these all, the most principle one in mulberry fruit is C3G and then C3R, also contains minimal amounts of pelargonidin-3-glucoside and pelargonidin-3-rutinoside, these two compounds, that is, cyanidin 3-O-(6’-O-α-rhamnopyranosyl-β-D-glucopyranoside) known as keracyanin and cyanidin 3-O-(6’-O-α-rhamnopyranosyl-β-D-galactopyranoside) have been identified by high-speed counter current chromatography [4].

Flavonols and flavanols: flavonols present in mulberry fruit include rutin, quercetin, quercetin 3-O-rutinoside, quercetin 3-oglucoside, quercetin 3-O-galactoside, myricetin, kaempferol, kaempferol 3-O-glucoside, and kaempferol3-O-rutinoside and flavanols present in it include catechin, epigallocatechin gallate, epicatechin, procyanidin B1, and procyanidin B2. Among all these, rutin is the most abundant one flavonols, quercetin, and kaempferol’s derivatives are its major components and their glycosylated forms, that is, quercetin 3-O-glucoside, quercetin 3-O-galactoside, and kaempferol3-O-rutinoside are found in some mulberry fruits [4].

Phenolic compounds and alkaloids: hydroxycinnamic acid and benzoic acid are two basic phenolic compounds in mulberry fruit. Compounds in hydroxycinnamic acid include chlorogenic acid, ferulic acid, p-coumaric acid, o-coumaric acid, and caffeic acid compounds in benzoic acid include gallic acid, p-hydroxybenzoic acid, syringic acid, protocatechuic acid, and vanillic acid. Among all these, chlorogenic acid occurs in the highest amount in mulberry, that is, 5.3–17.3 mg/100 g DW. Other major phenolic compounds include gallic acid, that is, 7.33–23.34 mg/100 g DW and cinnamic acid, that is, 11.64–15.05 mg/100 g DW. The concentration of phenolic compounds in different mulberries varies as geographical area and environmental factors, that is, temperature, light, humidity, and degree of maturity [4]. Alkaloids are pharmacologically active, therapeutic, and nitrogen-containing compounds [26]. In white mulberry, through NMR Spectroscopy, five alkaloids have been found, that is (morrole B, C, D, E, and F), and alkaloids present in other mulberry fruits include 2-formyl-5-(hydroxymethyl)-1H-pyrrole-1-butanoic acid, 5-(hydroxymethyl)-1H-pyrrole-2 carboxaldehyde, 2-formyl-1H-pyrrole-1-butanoic acid, and 2-formyl-5-(methoxymethyl)-1H-pyrrole-1-butanoic acid [27].

Aromatic and volatile compounds: Aromatic compounds, that is, benzaldehyde, ethyl butanoate, (E)-2-nonenal, 3-mercaptoethanols, and 1 hexanol are present in mulberry fruits [28] and volatile compounds present in white and black mulberry fruits include 2,4-nonadienal, methyl hexanate, limonene, octanol, and ethyl hexanoate [29].

Melatonin: A neurohormone also known as N-acetyl-5-methoxytryptamine, produced by the pineal gland, has a role in regulating circadian rhythms and sleep ailments and also possesses antioxidative and anti-inflammatory properties. Many fruits including mulberry have a good percentage, but the percentage differs as per fruit development, that is, high levels (5.76 ng/g FW) present in stage 1 and then decreased in stage 2 and 3 [4].

3.2 Nutrient composition of three major types

Mulberries are a great combination of bioactive compounds, that is, sugars (glucose and fructose), vitamins, minerals, fats (linoleic, palmitic, and oleic acid), and phenolic compounds, that is, alkaloids, flavonoids, tannins, and carotenoids [30].

M. alba: M. alba is a great composite of carbohydrates, lipids, proteins, vitamins, minerals, and fiber. The percentage of protein in M. alba is higher as compared to raspberries, strawberries, and blackberries [31]; it contains all essential amino acids, particularly branched-chain amino acids [21]; other than essential amino acids, M. alba also contains nonessential amino acids also its amino acid/total amino acid content is 42% that is equivalent to a good protein source, that is, fish and milk [32]. Macro and micronutrient composition of M. alba show that it contains 1.55 g/100 g dw protein, 0.48 g/100 g dw lipids, 1.47 g/100 g dw crude fiber, 0.57 g/100 mg dw ash content, 14.21 g/100 g dw total carbohydrates, moisture of fresh weight (fw) is 81.72 g/100 g dw, 7.55 g/100 g fw total sugar content, 0.088 mg/100 g fw riboflavin, 15.2 mg/100 g fw ascorbic acid, 0.19–0.37 g/100 g dw calcium, 0.24–0.31 g/100 g dw phosphorus, 1.62–2.13 g/100 g dw potassium, 0.12–0.19 g/100 g dw magnesium, 28.2–46.74 mg/kg dw iron, 4.22–6.38 mg/kg dw copper, 12.33–19.38 mg/kg dw manganese, 14.89–19.58 mg/kg dw zinc, 1.40–2,62 mg/kg dw nickel [33]. M. alba seeds are enriched with omega 3 fatty acids [34]. Upon analysis, its quoted that it contains the highest percentage of total fats, that is, 1.10%, followed by 0.95% in Morus nigra and then 0.85% in M. rubra [35] fatty acids composition shows that it contains linoleic acid and oleic acids in good amount along with this also contains trace quantities of eicosadienoic, linolenic, stearidonic, eicosanoic, and erucic acid [33]. The concentration of polyunsaturated fatty acids is highest in its fruit, that is, 76.68%, then monounsaturated fatty acids and lastly, saturated fatty acids [36]. Amount of total phenols is 0.13–0.40 mg GAE/g (fw), total flavonoids 29 mg/QE/100 g (fw), anthocyanins 0.36 mg/100 g (dw), carotenoids 13.16 mg/100 g, total sugars 7.55 g/100 g (fw), fructose 3.0–6.27 g/100 g (fw) and glucose 3.1–6.68 g/100 g (fw) [37]. Phytochemical investigation shows that it contains 5 anthocyanins (phenolic compounds serving as cancer-protective, cardioprotective, and inflammation-protective agents) and 25 phenolic compounds [38].

M. nigra: It has been used for medicinal purposes since ancient times because of its good compositional status comprising both nutritional and biologically active nutrients, that is, carbohydrates (polysaccharides), proteins, vitamins, minerals, and polyphenols, that is, anthocyanin and quercetin. Furthermore, extracts of this fruit also attain anti-Alzheimer, antimicrobial, antitumor, and anticancerous qualities [39]. Amount of moisture 82.40% (fw), ash 0.50% (dw), carotenoids 14.0 mg/100 g (dw), protein 0.96 g/100 g (dw), fat 0.95 g/100 g (fw), fiber 11.75 g/100 g (dw), total phenols 0.42–0.80 mg GAE/g (fw), total flavonoids 276 mg QE/100 g (fw), total sugars 6.64 g/100 g (fw), fructose 1.5–5.63 g/100 g (fw), glucose 1.4–7.75 g/100 g (fw), anthocyanins 0.57 mg/100 g (fw), riboflavin 0.04 mg/100 g (fw), niacin 1.6 mg/100 g (fw), ascorbic acid 11.30–15.37 mg/100 g (fw), iron 4.2–42.13 mg/100 g (fw), calcium 132 mg/100 g (fw), phosphorous 232 mg/100 g (fw), sodium 59 mg/100 g (fw), potassium 922 mg/100 g (fw), magnesium 106 mg/100 g (fw), and nickel 0.27 mg/100 g (fw) [37].

M. rubra: Its nutritional composition analysis shows that it contains 1.26 g/100 g (fw) protein, 0.85 g/100 g(fw) fat, 3.2–5.41 g/100 g (fw) fructose, 3.3–6.07 g/100 g (fw) glucose, 19.38 mg/100 g (fw) anthocyanins, 16.17 mg/100 g (fw) ascorbic acid, 4.5–57.38, 132 mg/100 g (fw) calcium, 226 mg/100 g (fw) phosphorous, 61 mg/100 g (fw) sodium, 834 mg/100 g potassium, 115 mg/100 g magnesium, 3.2–5.04 mg/100 g (fw) zinc, 0.37 mg/100 g (fw) nickel, 0.20–0.90 mg GAE/g (fw) total phenols, and 219 mg QE/100G (fw) total flavonoids [37].

4. Health benefits of mulberry fruits

M. alba is a great composite of bioactive compounds, and due to their presence, this fruit has been used in Chinese medicine for treating fever, optical disorders, upper respiratory tract problems, high blood pressure, hypercholesterolemia, and joint problems [40]. In 1985 Ministry of Health of China had titled this fruit to be the first one to provide curative benefits to health. Korean and Japanese also use this fruit for the treatment of sore throat, liver and kidney disorders, and eye health issues [4].

4.1 Antioxidative activity

An antioxidant exhibits radical scavenging effects [41], the ability to transfer its electron to the radical to establish cell neutralization [42] and thus possess an antioxidizing nature [23] for the physiological processes reduction in oxidative stress caused due to pollutants, alcohol, medicine, illness, poor diet, toxins, and radiations is very much important because oxidative mutilation to DNA (deoxyribonucleic acid) proteins and other macromolecules becomes a resourceful reason for many diseases [30].

The phenolic content commands the antioxidative activity of the mulberry fruit, dependent on the cultivator, phenotype, amount of phytochemicals in fruit and age; as the fruit reaches the maturity age from unripened to ripened, the phenolic content increases. A vast variety and good quantity of polyphenols in mulberry fruit offer surplus benefits. The antioxidative capacity of mulberry fruit polysaccharides (MFP) is amazing, among four fractions of MFP, that is, MFP-1, MFP-2, MFP-3, and MFP-4, MFP-4 possess the best scavenging properties [4], in vitro studies mulberry fruit polysaccharide, that is, MFP3P-Se (selenide of polysaccharide) showed great radical scavenging activity as compared to MFP3P [43]. Four mulberry species, that is, alba, rubra, nigra, and laevigata, when tested for phenol and alkaloid content, showed a higher content of these compounds, that is, (880 ± 7.20)-1650 ± 12.25 mg/100 g fresh weight and (390 ± 3.22)-660 ± 5.25) mg/100 g fresh weight, respectively [44]. Mulberry fruit anthocyanins possess antioxidative properties verified by mulberry juice purification (MJP) and mulberry mark purification (MMP) [45]. Other than anthocyanins, mulberry fruits also contains resveratrol, a potent antioxidant; that reduces reactive oxygen species [46] and ultimately reduces DNA damage [47].

Due to its great composition, this fruit acts very strongly in radical striking areas, mainly skin, tissue, hair, and other areas of the body, thus preventing the oxidate stress of these radicals and ultimately reducing blemishes, age-related spots and promoting healthy body status [48] also gains the ability to prevent premature white hair formation [23], possess the ability to destruct oxidative substances that have a role in damaging red blood cells [49]. In context to mulberry fruit protective action, 70% ethanol extract comprised of 400 μg/mL showed a positive action against H₂O₂-induced oxidative injury of pancreatic MIN6N beta-cells [37]. In streptozotocin-induced rats, mulberry fruits boost up the antioxidative defense mechanism and lower down damaging oxidative substances [49]. The antioxidative potential of black mulberry fruits was assessed by preparing methanol extract and using α, α-diphenyl-β-picrylhydrazyln(DPPH). Results concluded the existence of high-level antioxidative activity of methanol extracts. In another experimental study, ethanol-ethanol water (1:1) and water extracts of black mulberry reported great antioxidative activity [50].

4.2 Anti-inflammatory activity

Mulberry fruits contain cyanidin-3-glucodise (C3 G) reported to provide anti-inflammatory properties, thus inhibiting inflammation and endothelial distinction. Researchers have also reported that black mulberries contain flavonoids providing anti-inflammatory response; work against proinflammatory cytokines in mice serum [51]. In female mice, tumor growth was inhibited by cyanidin-3-glucoside, ultimately leading to apoptosis [22].

4.3 Antibacterial activity

S. epidermidis and placacnes places are the bacterias responsible for acne; black mulberry fruit possesses antibacterial properties against these bacterias and has been reported to prevent bacterial acne [52]. M. alba’s component; Morin, when investigated against bacterial activity, showed antibacterial properties against Streptococcus mutants [53]. Black mulberry possesses more antibacterial properties as compared to other mulberries, that is, studies revealed that flavonoids in black mulberry’s possess great antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus than flavoinds present in other mulberry types [54].

4.4 Antiobesity activity

Obesity is the basic root cause of many chronological disorders, that is, diabetes mellitus, cardiovascular diseases, and cancer. Around the world risk of obesity and its related disorders is now increasing at a great speed which is now a point of concern. Mulberry fruit has been known to provide antiobesity properties. A study was conducted on male hamster rats to determine the effect of mulberry fruit extract on body weight; results concluded a decline in the body weight status [51].

4.5 Antitumor activity

To identify the role of natural compounds in possessing antitumor activities, a series of detailed research has been done for this purpose and came to the point that mulberry fruit offers virtuous antitumor activities through different pathways, an important biological quality [4]. Mulberry fruit extract (MFE) antitumor activity is characterized by the decline in nitric oxide production in lipopolysaccharides (LPS) produced RAW 264.7 cells, MFE in LPS also suppresses the expression of proinflammatory markers and cytokines [55]. Another study in mice also reported a positive role of MFE in suppressing acute colitis and tumorigenesis, and in S-phase cell cycle arrest, phenolic components of MFE provide a 70–80% decline in tumor growth [56]. MFE contains a good percentage of anthocyanins and, when fed to mice for the period of 7 weeks with an objective to investigate tumor growth, results concluded a decline in Atypical Glandular Cells (AGS) tumor xenograft growth [57]. Other than anthocyanins, resveratrol present in mulberry fruit has been reported to decrease the proliferative mechanisms of tumor growth in lymphoid, myeloid, breast, prostate, stomach, colon, pancreas, thyroid cancers, and ovarian and cervical cells [58].

4.6 Antihyperglycemic activity

Diabetes mellitus, characterized by high blood glucose levels due to defects in the secretion of insulin [51] and other metabolic issues and has now become the third lifespan-threatening disorder. It is also estimated that the prevalence of this disorder will constantly increase rather than decreasing; it is also expected that 300 million patients will be diabetic by 2025. Natural food items have been evaluated a lot for the determination of hypoglycemic effects to manage hyperglycemia [4]; mulberry fruit contains 1-deoxynojirimycin (DNJ), glycopeptides, hydrophobic flavonoids, and 2-arylbenzofuran; serves important role in high blood glucose management [30] provision of DNJ and alpha-glucosidase inhibitors; this fruit is very much fruitful against diabetes [30]. Four mulberry fruit polysaccharides have been isolated, that is, MFP-1, MFP-2, MFP-3 and MFP-4; MFP-3 and MFP-4 possess better inhibitory effects on α-amylase and α-glucosidase than MFP-1 and MFP-2 [43].

A study concluded that when diabetic rats were given mulberry fruit polysaccharides – MFP50 and MFP90 ethanol extract for the period of 7 weeks revealed 26.5% and 32.5% reduction in serum insulin levels and glucose levels, respectively. Another study conducted on diabetic rats showed that when they were given ethyl acetate-soluble extract of mulberry for the period of 2 weeks concluded a decrease in the fasting glucose and glycosylated serum protein levels. In another study, mulberry anthocyanin extract (50 and 125 mg/kg body weight per day) was taken to investigate its effects on blood sugar levels of diabetic mice, extract was given for the period of 8 weeks and showed an effective reduction in fasting blood glucose levels [37]. In streptozotocin-induced diabetic mice, mulberry fruit extract (MFE) has been reported to hamper alpha-glucosidase activity, suppress fasting blood glucose levels, and suppress glycosylated serum proteins [59]. A study conducted on two fractions of mulberry fruit polysaccharides, that is, MFP50 and MFP90, for the period of 7 weeks reported a decline in fasting glucose and serum insulin levels [60]. Another study on Ramulus mori polysaccharide obtained from white mulberry concluded the reduction in fasting glucose levels in diabetic rats [61]. Research conducted on diabetic C57BL/KsJ-db/db mice to determine the effect of MFE containing anthocyanins showed that it has the capability to improve insulin sensitivity, to decrease glucose 6-phosphatase, to decrease phosphoenolpyruvate carboxykinase ranks in the liver [4]. In streptozotocin-induced type 2 diabetic rats, polysaccharides present in mulberry fruit demonstrated a very chief role, that is, repaired damaged pancreatic tissue, lowered fasting glucose levels, decreased fasting insulin levels, and increased high-density lipoprotein cholesterol [60].

In the rats model, antidiabetic activity of mulberry anthocyanins has been observed, that is, a reduction in fasting blood glucose levels and serum insulin levels [62]. Increase in insulin sensitivity, activated protein kinase (AMPK), and glucose transporter type 4 (GLUT 4) and reduction of fasting hyperglycemia, postprandial blood glucose, and glycated serum proteins. Has been seen in chemically induced diabetic mice model given white mulberry fruit extract [63].

4.7 Cardioprotective activity

Resveratrol present in mulberry fruit provides protection against various heart-related diseases, decreasing oxidants levels by reducing HO and AKT levels and by increasing Trx-1 and vascular endothelial growth factor (VGEF) levels [47]. Anthocyanins in mulberry fruit possess antihyperlipidemic characteristics, that is, in rat models, a reduction in cholesterol, triglyceride, and adiponectin levels has been observed after administering this fruit [62].

Hyperlipidemia is defined by excessive cholesterol, that is, LDL (low-density lipoprotein) and VLDL (very low-density lipoprotein), and fatty materials in the blood leading to the development of atherosclerosis. A study conducted on human beings aged (30–60 years) with an objective to determine the effect of mulberry fruit consumption on lipid profiles concluded a positive association between lipid profile and mulberry fruit consumption, that is, decreasing total cholesterol and low-density lipoprotein, suggesting it for individuals with hypercholesterolemia [4]. Water extracts of mulberry fruit indicate lipid-lowering benefits by decreasing biosynthesis and increasing the levels of the LDLR gene. The presence of linoleic acid and dietary fiber in mulberry fruit provides a very positive action against hyperlipidemia; research conducted on rats provided them with 5% or 10% mulberry powder with a high-fat diet concluded a decrease in LDL, liver triglyceride, and total cholesterol and increase in HDL (high-density lipoprotein). Consumption of 45 g freeze-dried mulberries for 6 weeks by hyperlipidemic adults aged (30 to 60 years) quoted a very positive result against hyperlipidemia [37].

In another study conducted on Wistar rats to investigate the hypolipidemic activity of mulberry fruit freeze-dried powder, Wistar rats along with mulberry were given with high-fat diet, and the results concluded that their serum triglyceride, total cholesterol, serum low-density lipoprotein, liver triglycerides, and atherogenic profile were reduced, and levels of high-density lipoprotein cholesterol were increased [4]. In a study, 45 g of freeze-dried mulberry fruits were given to hypercholesterolemic individuals for the period of 6 weeks; a reduction in low-density lipoprotein (LDL) was observed [64]. Mulberry fruit extract also possesses a property against the development of atherosclerosis; in a study, rabbits induced with a high-fat diet, when administered with MFE, showed a reduction in atherosclerosis [65].

4.8 Nephroprotective activity

Mulberry fruit also possesses nephroprotective activity; butyl pyroglutamate, a bioactive compound obtained from mulberry fruit effective against cisplatin-induced nephrotoxicity [37]. A study conducted on rabbits to investigate the nephroprotective properties of M. alba; results concluded that after administering 200 mg/kg/d of M. alba ethanol extract for the period of 2 weeks subject’s serum creatinine (4.02 ± 0.14, p < 0.0001), blood urea nitrogen (54.18 ± 2.60, p < 0.0001), and serum uric acid levels (2.34 ± 0.12, p < 0.001) were managed from the baseline results. Other than this, a decline in creatinine clearance and urinary volume was also reported [66].

4.9 Neuroprotective activity

Mulberry fruit consists of cyanidin-3-O-β-D-glucopyranoside; have a role in preventing neuronal cell damage and also prevents the cerebral ischemic damage caused by oxygen-glucose deprivation (OGD) in PC12 cells [67]. Researchers observed mulberry fruit ripening stages and found that ripened mulberry fruit possesses great neuroprotective potential due to the occurrence of high concentrations of phenolic compounds [68]. It also possesses antistress action by inhibiting plasma peroxide levels [37]. Its fruit extract, when tested in animal models with vascular dementia against memory impairment and brain damage, was observed that it is a very potent natural cognitive enhancer and neuroprotectant [69]. Mulberry fruit extract also contains Oxyreservatrol, a natural hydroxystilbene that provides a neuroprotective effect against neurodegenerative diseases caused due to oxidative damage such as Alzheimer’s disease, characterized by cellular damage, high lipid peroxidation and an increase in iron and aluminum levels [70]. Cyanidine-3-glucoside (C3G) fraction from M. alba possess neuroprotective potential, and when analyzed for oxygen deprivation and glutamate-induced cell death in rats, results concluded it possesses a protective potential against oxygen-depressed cellular loss not on glutamate-induced cell death [71].

Omega 3 and 6 are essential fatty acids important for the development of healthy cell membranes, and for boosting neural functions by the formation of hormones, eicosanoids, thromboxanes, leukotrienes, and prostaglandins [72]. The human body cannot synthesize these essential fatty acids, and thus exogenous source is required; mulberry fruit contains these fatty acids, which then provide strength to brain functioning and protection against cholesterol neurotoxicity [73]. In the mammalian central nervous system, dopaminergic neurons present in the midbrain are the chief source of dopamine (DA); loss of dopaminergic neurons leads to a neurological disorder, that is, Parkinson’s disease (PD) [74]. Mulberry fruit extract has been found protective for dopaminergic neurons against neurotoxicity, thus protecting against Parkinson’s disease, ultimately ameliorating chronic disorders [75]. In addition, mulberry fruit extract has been found supportive in rat models facing memory-related problems and hippocampal damage, that is, MFE improved their memory and also heightened the concentrations of neurons and cholinergic activity [76].

4.10 Gastroprotective activity

Mulberry fruit contains iron, riboflavin, vitamin C, vitamin K, potassium, phosphorous, calcium, dietary fiber, and phytonutrients, that is, zeaxanthin, resveratrol, anthocyanins, lutein, and polyphenolic compounds. Dietary fiber plays an essential role in the prevention of constipation, bloating, and cramping by adding bulk to the stool and by speeding up the movement of food through the digestive tract [77]. In experimental rats, gastric mucosal injury characterized by an observable fall in leucocyte infiltration to the submucosal layer was significantly reduced by M. alba extract [78]. M. nigra fruit’s oral administration of a high dose (300 mg/kg) is very potent against ethanol-induced acute gastric ulcers in female rats [79]. It has been reported in mice this fruit effectively prevented constipation; along with this, it also increased the concentration of acetic, propionic, butyric, isovaleric, lactobacillus, and bifidobacterium and decreased the occurrence of Helicobacter and prevotellaceae in feces [80].

4.11 Cancer-protective activity

Many medicinal plants exhibit protective properties against bacteria, virus, inflammation, and cancer, thus providing immune strengthening and antioxidative properties. Anthocyanins obtained from M. alba have shown inhibition of metastatic A549 human lung cancerous cells [81]. Phenolic compounds possess anticancer properties in in vitro hepatoma cells by arresting cell cycle at G2-M phase and by stopping topo-isomerase II activity [38]. International Agency for Research on Cancer (IARC) specialized agency of cancer by the World Health Organization (WHO), stated that 10 million deaths were caused due to cancer worldwide by 2020; Asia ranked in the top (58.3%), followed by Europe (19.6%) due to resistance to drugs and their side effects [82]. In animal tumor studies, phenols present in mulberry depicted anticarcinogenic mechanisms in different cancerous cells, that is, working as an antioxidant, an antiproliferative, and an antiangiogenic, thus leading to the induction of apoptosis. Anthocyanins such as cyanidin and pelargonidin present in M. nigra possess the ability to decrease the capability of cancerous cells and also possess the ability to hinder tumor growth [22]. Resveratrol present in mulberry fruit suppresses the activity of transcription factor 4EBP1 and also decreases the proliferation of cancerous cells in breast cells [51]. M. nigra; a well-known anthocyanin-rich fruit, possesses the quality of inhibiting the formation of stomach cancer caused by Helicobacter pylori; a prominent factor in causing stomach cancer [39].

4.12 Hepatoprotective activity

Accumulation of lipids in liver cells is the leading cause of the development of nonalcoholic fatty liver. In mice, hepatic steatosis caused by a hyperlipid diet has been improved by ethanolic extract of M. nigra fruits, that is, reduction in serum levels of ALT and AST, reduction in lipid droplets of liver cells, reduction in triglyceride and cholesterol levels of liver cells and reduction in fatty acid and cholesterol biosynthesis [83]. A study was conducted on three mulberry fruit polysaccharides, that is, MFP-I, MFP-II, and MFP-III, by adding 30%, 60%, and 90% ethanol; the mixture was then given to evaluate the efficacy of MFP against palmitic acid (PA) induced liver lipotoxicity, the study concluded MFP-II significantly decreased PA-induced liver lipotoxicity at 0.1 and 0.2 mg/ml and also enhanced catalase and glutathione peroxidase activities; protecting against PA-induced liver lipotoxicity [84].

5. Conclusion

This chapter focused on the fruit named mulberry, which is very known and commonly used around the world for its extraordinary health benefits. Many different types of mulberry plants exist, but this chapter focused on its three major types, that is, M. alba (white mulberry), M. nigra (black mulberry) and M. rubra (Red mulberry). These all are very well known due to great nutritional composition as composition shows the presence of phytonutrients & bioactive compounds, that is, anthocyanins, flavanols, flavonols, phenolic compounds, aromatic compounds, volatile compounds, resveratrol, cyanidin-3-O-β-D-glucopyranoside, cyanidin-3-glucodise (C3 G), butyl pyroglutamate, and melatonin. The presence of these phytonutrients and bioactive compounds made this fruit responsible for offering multiple health-promoting and protecting activities, that is, antioxidation, anti-inflmmation, antitumor, antibacterial, antiobesity, antihyperglycemic, cardioprotective, nephroprotective, neuroprotective, hepatoprotective, cancer-protective, and gastroprotective.

AGS

Atypical Glandular Cells

AMPK

Activated Protein Kinase

C3 G

Cyanidin-3-glucodise

DNA

Deoxyribonucleic Acid

GLUT 4

Glucose transporter type 4

HDL

High-Density Lipoprotein

IARC

International Agency for Research on Cancer

LDL

Low-Density Lipoprotein

LPS

Lipopolysaccharides

MFP

Mulberry Fruit Polysaccharides

MJP

Mulberry Juice Purification

MMP

Mulberry Mark Purification

PD

Parkinson’s disease

VLDL

Very Low-Density Lipoprotein

VGEF

Vascular Endothelial Growth Factor

WHO

World Health Organization

OGD

Oxygen Glucose Deprivation