Citrus: An Overview of Food Uses and Health Benefits

Abstract

Citrus species is a category of fruit that contains a variety of bioactive components throughout the plant. Citrus fruits (and items made from them) are among the most widely eaten fruits in the world, and their supply continues to increase. Oranges, pomelos, limes, tangelos, mandarins, lemons, kumquats, grapefruits, and other Citrus fruits are among them. They are frequently employed in the culinary, cosmetics, and pharmaceutical sectors due to their fragrance and taste. Vitamin C, pectin, limonene, phenolics, iso-limonene, flavanones, and nonanal are the main bioactive components present, and they provide a variety of health advantages. Pharmacological studies have shown that the fruit has numerous nutraceutical benefits, including a strong antioxidant, antidiabetic, anti-hypertensive, anticancerous, antibacterial, antifungal, antimicrobial, antihyperglycemic, and cardioprotective. It should also be highlighted that all Citrus fruits are an excellent source of minerals, which are required to maintain water and electrolyte balance. Citrus fruit-eating has been linked to a range of health advantages in recent research. This chapter presents an overview of the nutritional aspects of Citrus as well as its health benefits, which will be detailed.

1. Introduction

Citrus fruits are members of the Rutaceae family and are the most marketed natural product on earth. Citrus, also known by the Romance loanword agrumes (sour fruits), is one of the world’s dominant cultivars, with a feature of the application and acceptance significantly to human food [1]. Citrus, which is commonly grown in subtropical and tropical regions, is one of the largest and most significant crops. Annually, over 150 million tons of Citrus natural products are filled in more than 140 nations. According to Food and Agriculture Organization (FAO), Italy, Spain, Argentina, the United States, and Greece are significant exporters of fresh Citrus, while the main exporters of organic Citrus juices are Brazil, Israel, Costa Rica, the United States, Italy, Mexico, and Cuba [2]. Citrus natural products have been appreciated by people since ancient times. Citrus fruits are an important part of today’s diet since they are soft, easy to peel, and have juicy flesh with a distinct flavor. Many Citrus species, such as grapefruits (Citrus paradisi), mandarins (Citrus reticulata), lemons (Citrus limon), oranges (Citrus sinensis), Citrus clementina, and Citrus unshiu are consumed as juice or used for the development of new products all over the planet [3]. Citrus is popular due to its distinct flavor, taste, and scent, as well as its increased level of phenolics, vitamin C, and other nutritional properties [4]. Citrus belongs to the Citrinae subtribe, tribe Citreae, and subfamily Aurantioideae. Furthermore, the continuing ordered study seems, by all accounts, to be confounded and disputed, as a result of sexual suitability among Citrus species and other taxa, a frequency range of bud modifications, and apomixis (e.g., adventitious embryonic) [5]. Swingle and Reece and Tanaka’s taxonomy classifications for Citrus, which classified 16 and 162 species, respectively, are the most frequently accepted [6]. Fruit and vegetable-rich cuisines have been significantly linked to multiple therapeutic benefits and a decreased probability of having illness [7]. Citrus is one of the world’s most significant natural product crops, grown for both fresh juice production and food processing. Citrus fruits and commodities are quite common with significant economic and nutritional influence in both developing and developed nations due to inexpensive economic accessibility, and customer attitude toward the increasingly recognized potential health benefits [8].

Dietary choices have been related to a range of health outcomes, including high blood cholesterol, hyperglycemia, high blood pressure, and other major chronic degenerative conditions [9]. There is a huge necessity for nutritious meals that, in addition to providing nourishment, may improve the public overall health status. Fruits and vegetables are high in nutrients, anti-inflammatory compounds, and phytochemicals [10]. Aside from that, the demand for plant-based commodities is increasing in both emerging and developed countries [11]. Thus, we may employ specific fruits, such as citron (C. medica), in various formulations and benefit from their health capabilities in lowering the risk of numerous prevalent ailments. The World Health Organization (WHO) suggests, including 400 g of fruits, in your balanced meals. Consuming more Citrus fruits, vegetables, and whole grains has been associated with a decreased risk of numerous metabolic syndrome-related disorders, particularly malignancy, impaired glucose tolerance, coronary heart disease, and neurodegenerative diseases, according to deterministic, observational, and intervention studies [12]. These illnesses are essentially connected with serious and second-rate extensive irritation created by responsive oxygen species. The bioactive constituents included in whole grains, vegetables, and fruits protect cells against oxidative damage by neutralizing free radicals, hence lowering the prevalence of these disorders [13]. Citrus fruit species have been extensively researched for their bioactive content and medicinal properties. Oranges account for the majority of all Citrus production/exports, followed by lemons/limes (8%), grapefruit (7%), and tangerines/mandarins (one-third) [14]. Citrus fruits have gained popularity in recent years due to their health-promoting properties. A variety of active substances contained in Citrus natural products have been detached and portrayed, and their part in people’s well-being has been extensively researched. Citrus fruits’ significance in one’s nutrition, as well as the abundance of key bioactive compounds, such as ascorbic acid (AsA), carotenoids, and flavonoids, in Citrus fruits, and their therapeutic properties are discussed in this chapter.

2. Nutritional perspectives of Citrus

Citrus spp. is abundant in vitamin C and is low in cholesterol, salt, and fat, and has a relatively low average calorie value, which may be helpful for users worrying about being overweight. Citrus includes significant levels of carotenoids (some of which can be converted to vitamin A), folate, and fiber [15]. The macronutrient composition of some Citrus fruit is presented in Figure 1 [1].

Figure 1.

Nutritional composition of Citrus fruit [1].

The fruits are high in important nutrients, such as dietary fiber, and simple sugars, and often a variety of micronutrients, including thiamin, copper, riboflavin, vitamin B6, magnesium, niacin, calcium, potassium, folate, phosphorus, pantothenic acid, all of which have been required for health maintenance and proper development [16]. Additionally, studies were carried out to better comprehend the diversity found in nature phytonutrients, such as flavonoids, carotenoids, and limonoids. Epidemiological data and other investigations have revealed that all these active components have a broad range of biological consequences and they may serve to act as an intermediary between Citrus fruit consumption and sickness protection [17], such as hyperglycemia, cancer, osteoporosis, cataracts, and cardiovascular disease. The nutritional profile of various Citrus fruits is presented in Table 1 [1].

Nutritional characteristics	Lemon	Grapefruit	Orange	Tangerine
Energy (kcal)	29	42	47	53
Dietary fiber (g)	2.80	1.60	2.40	1.80
Protein (g)	1.10	0.77	0.94	0.81
Carbohydrates (g)	9.32	10.66	11.75	13.34
Cholesterol (g)	0	0	0	0
Total fat (g)	0.30	0.14	0.12	0.31
Niacin (mg)	0.100	0.204	0.282	0.376
Riboflavin (mg)	0.020	0.031	0.040	0.036
Pantothenic acid (mg)	0.190	0.262	0.250	0.216
Pyridoxine (mg)	0.080	0.053	0.060	0.078
Vitamin A (IU)	22	1150	225	681
Vitamin C (mg)	53	31.20	53.20	26.70
Vitamin E (mg)	0.15	0.13	0.18	0.20
Calcium (mg)	26	22	40	37
Potassium (mg)	138	135	181	166
Copper (μg)	37	32	45	42
Magnesium (mg)	8	9	10	12
Iron (mg)	0.60	0.08	0.10	0.15
Zinc (mg)	0.06	0.07	0.07	0.07
Manganese (mg)	0.030	0.022	0.025	0.039
α-Carotene (μg)	1	3	11	101
β-Carotene (μg)	3	686	71	155
Xanthophylls (μg)	11	5	129	138
β-Cryptoxanthin (μg)	20	6	116	407
Lycopene (μg)	0	1419	0	0

Table 1.

Nutritional characteristics for Citrus fruits per 100 g fruit [1].

3. Bioactive compounds of Citrus fruits

Citrus fruits are high in bioactive chemicals, particularly phenolic compounds (flavonoids, coumarins, and phenolic acids), terpenoids (carotenoids and limonoids), and pectin [3, 18, 19]. Citrus fruits are also high in nutrients, including ascorbic acid, tocotrienols, tocopherols, and minerals (iron, manganese, zinc, selenium, and copper) [3, 18, 19]. Flavonoids, which are a significant source of antioxidants in the diet of humans, are a kind of polyphenolic compound abundant in Citrus fruits. Flavanones account for approximately 95% of the total flavonoids generated by Citrus [20]. Citrus-derived flavonoids can be aglycones or glycosides, and they as a rule do not happen in nature as aglycones yet rather as glycosides, in which the aglycones are linked to a sugar molecule [21]. Citrus fruits contain a significant quantity of flavonols (kaempferol, quercetin, and rutin), polymethoxylated flavones (e.g., 5-dimethyl nobiletin, tangeritin, and nobiletin,), flavanone-7-O-glycosides (narirutin, naringin, eriocitrin, and hesperidin), flavones (e.g., vitexin, diosmin, and rhoifolin,), and anthocyanin (peonidin glucosides and cyanidin) [22, 23]. When contrast to other Citrus species, C. aurantium has a higher concentration of active alkaloids, particularly synephrine, which accounts for more than 85% of the total alkaloid value [24]. The most common limonoids due to the dominance of Citrus species are limonin and limonin glucoside. Carotenoids are a type of isoprenoid pigment that is widely used in photosynthesis and signaling [24]. Citrus fruits’ peel and pulp are orange-red owing to the existence of carotenoids and apocarotenoids [25]. Citrus fruits’ carotenoid content is by carotenoid fatty acid esters (xanthophyll esters) [25, 26]. The bioactive compound of Citrus is presented in Table 2 [1].

Fruit	Metabolites	Flavonoid	(mg/100 g)
Grapefruit	Flavanones	Naringenin	21.34
		Eriodictyol	0.65
		Hesperetin	2.35
	Flavonols	Quercetin	0.40
		Myricetin	0.05
Grapefruit, pink and red	Flavones	Luteolin	0.60
	Flavonols	Quercetin	0.33
		Kaempferol	0.01
		Myricetin	0.01
	Flavanones	Naringenin	32.64
		Hesperetin	0.35
Grapefruit white	Flavanones	Naringenin	31.18
Lemons	Flavonols	Quercetin	1.14
		Kaempferol	0.03
		Myricetin	0.50
	Flavanones	Naringenin	0.55
		Eriodictyol	21.36
		Naringenin	27.90
	Flavones	Luteolin	1.90
Lime	Flavonols	Quercetin	0.40
	Flavanones	Naringenin	3.40
		Hesperetin	43.00
Orange	Flavonols	Quercetin	0.45
		Kaempferol	0.13
		Myricetin	0.15
	Flavanones	Naringenin	15.32
		Hesperetin	27.25
		Eriodictyol	0.17
Tangerine	Flavanones	Naringenin	10.02
		Hesperetin	7.94

Table 2.

Bioactive substance of Citrus fruits [1].

The existence of specific total carotenoids & xanthophyll esters is strongly impacted by species, maturation stage, and fruit components. Tangerines and oranges contain substantial amounts of β-cryptoxanthin, zeaxanthin Lutein, and β-carotene [27].

The carotenoids found in the endocarp and flavedo of completely developed oranges were (all-E) and (9Z) violaxanthin, which were esters and monoesters containing myristate, palmitoleate, caprate, stearate, palmitate, oleate acyl moieties & laurate, lutein, β-carotene, and antheraxanthin were the other important carotenoids. In contrast, violaxanthin, β-carotene, α-carotene, and lutein were shown to be plentiful in ripe green fruit, furthermore, β-citraurin esters were discovered in Citrus fruit flavedo [28]. Citrus fruits’ provitamin a carotenoids (e.g., β-cryptoxanthin) have also been found to help with metabolic disorders, such as type 2 diabetes [29]. Hesperidin (HSP) is a potent bioactive flavonoid aglycone and subclass of flavonoids found in Citrus species (lime, orange, lemon, and blood orange) [30]. This flavanone has been demonstrated to have a variety of pharmacological actions, including antiviral activities, anticarcinogenic, anti-inflammatory, and antioxidant properties, analgesic [31], hypolipidemic, hypoglycemic activities, and anticoagulant [32].

4. Health perspectives

Citrus fruit has natural compounds, which offer a wide range of bioactivities, including antimicrobial, anti-sensitivity, antioxidant, and anti-disease capabilities, as well as heftiness, hepatoprotective, neuroprotective, and cardiovascular regulating qualities. The different medicinal characteristics of Citrus are layout in Figure 2.

Figure 2.

Health benefits of Citrus and its constituent [27, 33, 34, 35, 36].

4.1 Citrus fruits and (COVID-19)

The potential significance of diet in the mitigation of coronavirus infection 2019 (COVID-19) has been undervalued so far among the different options. Foods contain usually compounds that may have a health benefit, and some of these chemicals may have antiviral properties and may be useful in altering the immune function and source of antioxidants from the oxidative stress generated by infection [37]. Citrus fruits are high in flavanones, vitamin C, and anthocyanins the most abundant of which are naringin and hesperidin, both of which have antioxidant and anti-inflammatory qualities [38, 39, 40]. Fibers, such as pectin, which is more abundant in the solid section, aid in the regulation of intestinal activities and the prevention of LDL cholesterol absorption. Citrus may also be effective in reducing the risk and cure of viral diseases [37].

The revelation that hesperidin possesses a chemical-physical structure that allows it to attach to critical proteins involved in the SARS-CoV-2 virus’s activity has piqued scientists’ curiosity. At least six investigations returned similar outcomes [41, 42, 43, 44, 45].

Wu and collaborators [41] for binding to SARS-CoV-2 proteins, evaluated 1066 natural compounds with the ability of antiviral effects, along with 78 antiviral medicines that have previously been described. The best option for bonding to the "spike" was hesperidin. At the point when the ACE2 — RBD complex is superimposed over the hesperidin — RBD complex, there is critical hesperidin contact with the ACE2 interface, showing that hesperidin may alter ACE2’s interaction with RBD. Another thorough molecular docking investigation of the hesperidin-Mpro interaction was published recently [44]. The lowest binding energy (showing the most affinity) was revealed to be rutin (9.55 kcal/mol), followed by hesperidin (9.02 kcal/mol), emetine (9.07 kcal/mol), ritonavir (9.52 kcal/mol), and indinavir (8.84 kcal/mol) in a screening of 33 natural and already known antiviral compounds. THR45, THR25, THR24, CYS145, HIS4, and SER46 are among the amino acids to which hesperidin forms hydrogen bonds. Joshi et al. research provided more evidence [45], who discovered hesperidin as one of the numerous natural compounds that adhere to the primary protease of the SARS-CoV-2 virus. In addition, the viral receptor angiotensin-converting enzyme-2 is involved (ACE-2).

As a powerful antioxidant against superoxide and hydroxyl radicals, hesperidin plays an important role in antioxidant defense mechanisms [46], and hesperetin, a derivative of it, prevents LPS-stimulated microglial cells from producing nitric oxide [47]. Another research found that Citrus flavanones, such as naringenin and hesperidin, reversed age-related decreases in superoxide dismutase, catalase, and glutathione reductase in the livers of elderly rats [48]. Coronaviruses are one type of virus that causes the common cold, a condition for which there is no treatment or vaccination. Given the fact that SARS-CoV is a coronavirus, as well as the low cost and high security of fresh foods with high doses of vitamin C, it has been proposed that boosting regular consumption of these foods may be advantageous during the COVID-19 pandemic [49, 50, 51]. Figure 3 shows hesperidin and L-ascorbic acid reduces the cell pattern of the SARS COVID-2 (SARS-CoV-2) infection, as well as the regions of infection, started cell, and fundamental illness (set apart with an "X") [37].

Figure 3.

Hesperidin and vitamin C impact on infected cell cycle [37].

As well as aiding the development of collagen in connective tissue, L-ascorbic acid has antioxidant capacity, and when combined with other minerals, enzymes, and vitamins, can lessen the effects of free radicals. Human vascular smooth muscle cells are considered to be protected by vitamin C from apoptosis by preventing LDL oxidation [52]. Citrus fruits may have a substantial impact on COVID-19 therapy, through pathways other than viral replication suppression and antioxidant activity [37]. The numerous biological effects of vitamin C and hesperidin are two core aspects of Citrus fruits that appear to be excellent choices for counteracting SARS-CoV-2 cell infiltration and modulating the disease’s systemic immuno-pathological stages. The more epidemiological, preclinical, and clinical study is required to verify the concept that a diet rich in Citrus fruits or comparable compounds may help COVID-19 prevention efforts [37].

4.2 Antioxidant activity

The primary source of reactive oxygen species (ROS) is oxygen, in living organisms through a variety of metabolic routes, such as hydroxyl radicals, hydrogen peroxide, and superoxide anion, while antioxidant systems may combat them to maintain equilibrium [53]. However, contemporary lifestyle variables may increase the number of reactive oxygen species, which play an important role in the development of different diseases, such as inflammation, heart disease, arthritis, aging, and cancer, and produce oxidative stress. Citrus extracts, including Citrus bergamia juice extracts, karna peel extracts, and Citrus limetta peel extracts, have been demonstrated to have antioxidant activity [33, 34]. Citrus fruits are said to be high in antioxidants because they contain phenolic compounds with poly-hydroxyl groups, such as flavonoids, phenolic acids, and their derivatives [54]. The following are the major antioxidant mechanisms:

• Direct absorption and neutralization of free radicals.

• Suppression of ROS-related enzymes: xanthine oxidase, myeloperoxidase, and NADPH oxidase [55].

• Increased activity of mammalian antioxidant enzymes, such as superoxide dismutase, catalase, and others [56].

4.3 Hepatic protective effects of Citrus fruit

The liver, the body’s most significant digestive organ, is responsible for toxic compound metabolization via several routes, such as hydrolysis, oxidation, reduction, conjugation, and hydration [57]. Lipopolysaccharide (LPS) is a glycolipid of gram-negative bacteria’s cell wall [16]. LPS raises total bilirubin levels, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Tissue and serum nitrite levels, as well as thiobarbituric acid reactive substances (TBARS) levels, increased, whereas superoxide dismutase (SOD) and glutathione (GSH) content decreased. However, hesperidin injection restored all of these abnormalities, and the authors concluded that hesperidin might reduce nitric oxide and reactive oxygen species (ROS) formation and prevent LPS-induced hepatotoxicity [17].

4.4 Anti-inflammatory

Inflammation is a complicated process characterized primarily by inflammatory cytokines, such as interleukin-6, tumor necrosis factor-alpha (TNF-α), interleukin-1β, and also a chain of molecular messengers, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These inflammatory cytokines have also been linked to the development of several inflammatory disorders, particularly colorectal cancer, Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease [35]. Orange (Citrus aurantium L.) isolate has been shown to inhibit UVB-induced COX-2 expression and prostaglandin (PG) E2 generation in HaCaT cells while also acting as a PPAR-c agonist [58]. Citrus fruit contains volatile oil coumarin and flavonoids, which have anti-inflammatory properties and can be utilized as a remedy to prevent or treat chronic inflammatory illnesses.

A meal incorporating 0.1% rutin, in particular, alleviated dextran sulfate sodium (DSS)-induced colon inflammation in mice, increasing histological ratings and mitigating weight loss, presumably via lowering pro-inflammatory cytokine production [59]. Furthermore, studies suggest that quercetin (50 and 100 mg/kg) treatment lowered structural, clinical, and behavioral outcomes in rats’ colons [60]. Isoquercitrin, a flavonoid with anti-inflammatory properties and antioxidants, is a glycoside that is chemically related to quercetin. This flavonoid reduces the levels of cyclo-oxygenase-2 (COX-2) and iNOS in rats, which helps them recover from acute colitis [61]. Kumar et al. observed that administering naringin at various dosages decreased acetic acid-induced colitis in animal models by decreasing DNA damage and inflammatory responses [62]. Naringenin is abundant in Citrus and has been extensively researched for its potential efficacy in several animal models of inflammatory illness. Apigenin is a flavone that may be found in a variety of fruits and vegetables, with grapefruit having the highest concentration. Its potential to relieve symptoms of inflammatory diseases is considered to be due to both anti-inflammatory and antioxidant properties. This was achieved by activating the aryl hydrocarbon (Ah)-receptor, which in turn produced good protective enzymes and cytokines, resulting in an improvement in the anti-inflammatory system [63]. Diosmin, a Citrus flavone recognized for its anti-inflammatory, antioxidant, and vasotonic effects, has also been researched for its potential to attenuate experimentally-induced colitis in animal models [64]. Among flavones, luteolin has proven tremendous anti-inflammatory efficacy in lots of experimental models. Luteolin inhibited intracellular inflammatory send signal in HT-29 colon epithelial by downregulating the Janus kinase (JAK)/sign transducer and activator of transcription (STAT) pathway [65]. Nobiletin and tangeretin are polymethoxylated flavones determined in Citrus, which have been established to assist in inflammation in many studies. In each in vitro and in vivo experiments, nobiletin suppressed inflammatory processes, along with the suppression of iNOS and COX-2 expression, and repaired the impaired intestinal barrier characteristic in trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and Caco-2 monolayer inhibiting the protein kinase b (Akt)-NF-jB-myosin light-chain kinase (MLCK) pathway affects the latter [66].

4.5 Anti-cancer

Secondary metabolites in Citrus fruits, such as coumarins, limonoids, and flavonoids, have been linked to a lower risk of cancer, including lung tumorigenesis, colonic tumorigenesis, breast cancer, hematological malignancies, gastric cancer, and hepatocarcinogenesis, among others [66, 67, 68, 69, 70]. Chang and Jia observed that the flavedo fraction of organ (Citrus reticulata cv. Suavissima) inhibited tumor growth by blocking epithelial-to-mesenchymal transformation and interfering with the (transforming growth factor-β1) TGF-β1–SMAD (Suppressor of Mothers against Decapentaplegic) Snail/Slug axis [71]. Citrus may lower cancer by inhibiting oxidative stress and damage, as well as interfering with cancer initiation, development, and progression [72]. Citrus bergamia (bergamot) juice has subsequently been revealed to exhibit anti-cancer potential in several in vitro and in vivo studies, with the flavonoid content attributed to this effect [73]. Vitamin C has been suggested to combat inflammation and consequent oxidative damage to DNA, both of which have a role in the beginning and progression of cancer. Furthermore, because of its pro-oxidant activity, vitamin C can destroy cancer cells [36].

4.6 Cardiovascular protection properties

Several recent epidemiologic studies commonly correlate greater flavonoid-rich food consumption to lower cardiovascular morbidity and mortality [74]. Several studies have demonstrated that Citrus-derived flavonoids may reduce triglyceride levels (TG) and blood cholesterol (CH). Using HepG2 cells, the optimum structure was found to be complete methoxylation of the A-ring of Citrus flavonoids for expressing a profound impact on regulating hepatic metabolic activity by decreasing apoB-containing lipoprotein production [75]. Nobiletin and tangeretin, which have the ideal chemical composition, may reduce blood triglycerides, but several Citrus flavonoids, such as naringin and hesperidin, that lack a methoxylated A-ring might have little or no lipid-lowering activity in vivo [76].

4.7 Impact on hyperglycemia

Citrus flavonoids (naringin, nobiletin hesperidin, and neohesperidin) reduced amylase-catalyzed starch digestion considerably. Furthermore, neohesperidin and naringin hindered only amylose digestion, but nobiletin and hesperidin inhibited both amylopectin and amylose metabolism. This research shows that Citrus flavonoids had an essential part in avoiding hyperglycemia development, in part by interacting with starch, improving hepatic metabolism and glycogen content while inhibiting hepatic gluconeogenesis [77]. Naringin, hesperidin, and nobiletin were also shown to have anti-diabetic properties, perhaps through increasing insulin sensitivity or increasing hepatic gluconeogenesis in hyperglycemic mice [78]. According to one research, streptozotocin nicotinamide-induced experimental in diabetic rats, naringenin protects against diabetes by exerting antihyperglycemic and antioxidant properties [79]. Chronic naringenin therapy in diabetic animals might avoid functional alterations in vascular reactivity via a prostaglandin-independent and NO-dependent mechanism [80].

5. Citrus byproducts utilization

Citrus juice, the principal product of processing firms is strong in vitamin C and is frequently employed in the production of nutrient-dense drinks. A large portion of this garbage is thrown on nearby landfills or burnt, resulting in contamination and a decrease in the dissolved oxygen concentration of contaminated water. The best way to handle these residues is to extract macro and micronutrients from by-products, use fiber-rich components in confectionery goods, fortify nutrient-rich animal feed, and bio-oils, and produce organic fertilizers, ethanol, and essential oils [81].

Citrus peel wastes are partially utilized in livestock feed, either fresh or after dehydration, but a significant amount of Citrus pulp is ended up lost in the fresh state owing to the complexity of handling and disposal of a significant amount of garbage generated in a very short period, and a considerable portion of it is nevertheless discarded into the atmosphere, possibly creating several ecological difficulties. As a result, the disposal of these Citrus by-products is a major issue for the Citrus industry all over the world [82].

Many studies are available on the handling of Citrus trash for the extraction of organic value-added substances, such as fiber and bioactive chemicals, such as flavonoids [83]. After processing Citrus fruits, more than 60 thousand tons of Citrus pomaces (CPs) are generated in South Korea each year. Public demand for non-synthetic, better natural food raw materials has fueled research into the recuperation of natural value-added chemicals from Citrus trash [84].

Citrus waste phytochemicals and value-added substances are used in the development of healthful meals, flavoring enhancers in food processing, health and power beverages, preservatives, and vitamin supplements. These aid in improving the flavor and scent of meals as well as correcting inadequacies. Citrus waste-derived phytochemicals are also used in skin, hair, and nail care products, as well as antibacterial antifungal lotions, toiletries, fragrances, and soaps [85].

Mucilage & pectin are elevated chemicals generated from Citrus waste. Pectin is a natural vegetable substance that is useful as a cosmetic and nutritional supplement, in pharmaceutical sectors owing to its stabilizing, thickening, and gelling qualities [86]. They are starches classified as "dietary fiber." Mucilages are the soluble dietary fiber that may be discovered in Citrus waste as well as other plants. They are also vegetable polysaccharides that are identical to pectin but varied in their uronic acid and sugar content. They, like pectin, may be employed in the culinary, nutritional, cosmetic, and pharmaceutical industries; new research has emphasized the anti-inflammatory properties of lemon mucilage [87].

Flavonoids, which are known antioxidants and are abundant in fruits and vegetables, are another fascinating substance that may be derived from Citrus trash. The same is used in both the pharmaceutical and food industries. Hesperidin, which can be isolated from orange and lemon peel, is particularly useful in the pharma industry due to its anti-inflammatory and vasodilatory effects [87].

Citrus trash may be converted into limonene, ethanol, and other byproducts. Limonene is used as a flavoring ingredient for medicinal purposes, and it has several applications in the chemical sector and home items. Citrus trash also contains a significant quantity of coloring pigment. They are possible sources of natural clouding agents, which are widely used in the soft drinks industry [85].

The solid residue may be used to extract essential oils, while the liquid can be utilized to make enzymes. Separation of hydrophobic substances from the skin may be used to make biodegradable polymers, packaging material, and food-grade kraft paper, reducing the requirement for petroleum-based polyesters [81].

6. Citrus fruit toxicity and safety profile

In animal toxicological testing, bioactive chemicals obtained from Citrus fruits demonstrated a high level of security. Hesperidin extracted from C. Sinensis dried peel revealed a modest reported adverse impact level of 1 g/kg, and a median fatal dosage of 4.83 g/kg, Sprague–Dawley rats were subjected to a 90 day subchronic and acute oral toxicity study [88]. This dose is substantially smaller than the flavonoids employed in animal research to offer the (10–200 mg/kg) same therapeutic effects, suggesting an excellent safety profile in the animals. Furthermore, additional Citrus flavonoids, such as tangeretin, nobiletin, and naringin, have demonstrated satisfactory effectiveness and safety [89, 90]. Limonene and other terpene-rich Citrus taste molecules, including oil, essential oil, peel extract, and whole fruit extract, are usually believed to be harmless [91].

7. Food-drug interaction

Grapefruit juice, for example, has an identical moniker in the context of high food-drug interaction by changing the normal working of the cytochrome oxidase mechanism. Grapefruit juice (GFJ) and HMG-CoA reductase inhibitors, sometimes referred to as statins, have the most well food-drug interaction. Grapefruit juice, when consumed in high quantities (32 oz. a day), can block the cytochrome P450 3A4 (CYP3A4) enzyme and raise serum levels of medications processed by this route, such as some statin medicines [92]. Many researchers have identified drug-GFJ interactions caused by suppression of CYP3A enzymes, a subclass of cytochrome oxidase enzyme system [93]. Furanocoumarins (in GFJ) specifically inhibit gastrointestinal CYP 3A4, increasing the oral bioavailability of medicines that are CYP 3A4 substrates, such as felodipine and cyclosporine, and eventually causing toxicity [94].

8. Future prospective

Oral supplementation delivery is acknowledged as the easiest, most efficient, and least expensive method for a broad range of medicinal significance [95]. Because of their heavy proportion in Citrus, bioflavonoids, such as naringenin, hesperidin, naringin, and polymethoxyflavones (PMFs) have been intensively investigated and encapsulated, and have illustrated medicinal characteristics in vitro and in vivo studies. Oral ingestion using novel encapsulating techniques, such as emulsification, liposomal interactions, hydro-gelation, nanoparticles, and membranes revolutionized the nutrition delivery mechanism [96]. Modern encapsulation techniques are developed to conserve bioflavonoids while improving target dispersion for medicinal benefits. The rapidly expanding worldwide food encapsulation business has shown higher demand and public knowledge of health additives and preventative measures for numerous diseases [92]. New unique delivery techniques must be developed to expedite the simple availability of Citrus bioflavonoid for medicines. Future studies, on the other hand, would need to blur the lines between the laboratory and the customer by boosting output and enhancing shelf life.

9. Conclusion

Citrus contains a variety of secondary metabolites, including phenolic acids, alkaloids, coumarins, flavonoids, carotenoids, limonoids, and volatile chemicals, which give a rational foundation for a variety of biological functions. Flavonoids, particularly methoxylated, flavones and flavanonols, and flavanones have greater bioactivities than other secondary metabolites. All of these active forms, however, operate together to give antimicrobial, antioxidative, anti-cancer, anti-inflammatory, hepatoprotection, neuroprotection, cardiac protection, and other advantages. Citrus are beneficial fruits to eat daily because of having multiple active forms with varied biological properties, both for their nutritive value and as chemotherapeutic or additional medication to promote health. Citrus fruit has various applications in the food industry. It can be used in the production of various food products. The bioactive compound, which is extracted from Citrus may be used in food additives, as stabilizers, thickeners, emulsifiers, preservatives, food colorants, and for many other purposes.

Acknowledgments

We are thankful to the digital library of GCUF for providing us with access to the publication.

Conflicts of interest

We have no conflict of interest.