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BY 4.0 license Open Access Published by De Gruyter Open Access January 10, 2023

Role and mechanism of fruit waste polyphenols in diabetes management

  • Faiqa Malik , Aqsa Iqbal , Sabika Zia , Muhammad Modassar Ali Nawaz Ranjha , Waseem Khalid , Muhammad Nadeem , Samy Selim , Milad Hadidi , Andres Moreno , Muhammad Faisal Manzoor , Przemysław Łukasz Kowalczewski EMAIL logo and Rana Muhammad Aadil EMAIL logo
From the journal Open Chemistry


Among various diseases in humans, diabetes is one of the most complicated disorders resulting either from the malfunctioning of β cells, causing a poor discharge of insulin from them, or poor functioning of the liberated insulin. A wide array of chemical compounds so-called secondary metabolites are present in plants. These phytochemicals are produced as by-products of metabolism and play a key role in plant protection. However, in humans, they offer several beneficial functions. Polyphenols are an important class of phytochemicals and apart from fruits, they are also found in their major wastes mainly including the peel, pomace, and seed. The current review is aimed to focus on the potential sources, distribution, and extraction/isolation of polyphenols from major fruit wastes along with highlighting their medicinal and therapeutic benefits, especially in the management of diabetes.

Graphical abstract

1 Introduction

The present era dominates with human beings’ victimization to a non-ending list of various diseases. Among these cardiovascular diseases, hypertension, obesity, diabetes, cancer, osteoporosis, and others of genetic origin are most common and often reported [1].

Diabetes, a chronic disease is characterized by hyperglycemia or increased levels of glucose in the blood, is a complicated disorder that results from poor secretion or inadequate functioning of insulin, dysfunctional β-cells, and irregularity in the metabolism of fat and glucose, leading to the damage and failure of major bodily organs, especially kidneys, heart, eyes, and others [2]. It has been reported that the prevalence of diabetes across the globe by 2019 is estimated to be 9.3% which is likely to rise to levels as high as 10.2 and 10.9% by 2030 and 2045, respectively. The reported figure predicts that in the future one in ten adults would be victim of diabetes mellitus [3,4].

Plants have been used for medicinal purposes for a long ago [5,6,7,8,9,10]. In line with the modern developments in the area of optimal nutrition, now there is a revival of interest in the use of plants as a source of food and medicine [11,12,13,14,15,16]. Plants produce a wide array of chemical substances that are crucial for their defensive mechanism [17]. These chemical substances of plants are categorized as primary and secondary metabolites. The secondary metabolites are the products of metabolism and possess various medicinal and therapeutic benefits, thus playing an essential role in curing serious ailments in humans. Among these secondary metabolites, polyphenols are of great importance [18].

Polyphenols are recognized by the presence of phenolic ring in their structure and actual are the heterogeneous group of phytochemicals that exhibit antioxidant, anti-inflammatory, and anti-diabetic properties [19,20,21]. In diet, polyphenols act as antioxidants [22]. Several thousands of polyphenols have been discovered, and owing to the number of phenolic rings, they are composed of several classes, but the most important and common classes of polyphenols include phenolic acids, flavonoids, tannins, lignans, and coumarins [23].

Polyphenols are isolated from various parts of plants like barks, roots, leaves, flowers, and even in the plant products, especially the fruits and vegetables. Among the fruits, the polyphenols’ richest sources are mango, banana, watermelon, camu-camu, passion fruit, citrus fruits, papaya, grapes, apple, pomegranate, and many more. During the processing of fruits, a huge quantity of waste is generated, ranging between 25 and 30% and mostly includes the peel, pomace, and seed/kernel [24]. Different studies have reported that the inedible constituents of fruits contain significant amounts of polyphenols compared to the edible portion that includes the pulp [25,26]. The polyphenols’ structural configuration may be significant potential for the cure of diabetes mellitus, particularly for type 2. Various plant-based natural drugs and polyphenol-rich phytomedicinal extracts are used nowadays to inhibit the activities of starch catalyzing enzymes and the glucose transporters in the body responsible for the elevated levels of glucose in the blood [27,28,29,30,31,32,33,34].

In perspectives of value addition, currently, there is increasing interest on the exploration of under-utilized fruit processing agro-wastes (such as peels) for the isolation of high-value bioactives and volatile oils [35,36]. Currently, world over interest is developed to extract valuable compounds from under-utilized agro-wastes so as to explore their commercial uses in cosmetics, medicines, and food preservation. The under-utilized fruit processing waste, especially peels of many fruits, is a potential source of several bioactive such as phenolics, flavonoids, tannins, and specifically limonoids, which are rare to other plants. These bioactive have important biological activities, including antioxidant, antimicrobial, anti-inflammatory, and anticancer [28,29,30,37,38,39].

As a result of fruit consumption and processing at large scale, world over, a huge quantity of fruit wastes, such as peels, seed, and rind, is produced annually that can be explored for value addition by the revalorization of these materials. Due to the lack of processing and storage facilities, the generated fruit waste is discarded to landfills instead of being useful. Emphasis must be laid on the proper processing of fruit wastes so that useful bioactive constituents can be extracted for the revolarization of such under-utilized agro-wastes. Afterward, it is utilized for various anti-diabetic medicine formulations that can play major role in combat diabetes and other disorders linked.

The disposal of the low-value by-products and waste generated by the fruit processing industries is a worldwide issue. The fact that the majority of this trash ends up in landfills raises environmental and societal issues [40]. The vast majority of these by-products are rich in nutrients, including antioxidants, carbohydrates, dietary fiber, polyphenol, vitamins, and minerals. Poly-phenols have a broad range of applications in several sectors, including food, cosmetics, fertilizers, animal feed, and pharmaceuticals [41,42,43]. Thus, the recovery of highly valuable polyphenols from fruit waste through the use of efficient extraction techniques will not only provide enormous health benefits to humans by substituting them in the development of nutritious products but will also serve as a source for reducing environmental pollutants. Specifically, it will provide new business and employment prospects.

Plants contain a wide variety of various bioactive compounds that in actual are the products of metabolism. These compounds are either termed as phytochemicals. Plant tissues of fruits and vegetables are a great source of phytochemicals that are in the form of phenolic compounds (PCs) [44]. Secondary metabolites of plants that are derived from shikimate-derived phenylpropanoid and/or polyketide pathway(s), consisting of more than one phenolic ring in their structure and without any nitrogen-based functional group [45]. Polyphenols are a group of secondary metabolites; literature reports significant potential of polyphenols against various diseases [46]. In plants, these biologically active components strengthen the defensive mechanism and have nothing to do with plant nutrition. In the plant kingdom (right behind cellulose), the second largest group of organic compounds are PCs and they have a variety of functions in the plant, such as protection from UV solar radiation, pathogens, biotic or abiotic stress, structural support, and herbivores. In humans, they offer several benefits ranging from the prevention of disease to its management [23]. In addition to their protection as antioxidant activity, PCs regulate a variety of physiological processes at many levels, such as enzyme inhibition, gene expression modification, and protein phosphorylation.

Polyphenols are phytochemicals that have the ability to improve one’s health. Flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules are the two types (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins) [47].

Polyphenols being the most extensive class of phytochemicals are further divided into the following subclasses [37,48]:

  1. Phenolic acids,

  2. Flavonoids,

  3. Tannins, and

  4. Coumarins.

2 Phenolic acids

The polyphenolic compounds contain one phenyl ring with minimum one carboxylic acid group [49]. The chemical configurations of phenolic acid depend upon the C1–C6 backbone. Phenolic acids are the main diverse group of polyphenols produced by plant sources. Phenolic acids are associated with sugars or organic acids and usually are components of composite configuration such as lignin and hydrolyzable tannins. There are two subclasses as benzoic acid contains the C1–C6 backbone and cinnamic acid contains the C3–C6 backbone. Various kinds of 8,000 phenolic acids have been recognized until now. They occur in a higher amount of various parts of the plant [50]. Phenolic acids are found in a variety of plants, both edible and non-edible and are biologically active compounds. Because of their antitumor, anti-inflammatory, antimicrobial, and antiaging properties, these compounds have commercial value in the medicinal, health, and beauty industries [51].

2.1 Fruit peel as potential source of phenolic acids

High contents of phenolic acids have been found in the peel of different fruits like pawpaw, mango, watermelon, apple, pomegranate, banana, orange, pineapple, and many others. Based on the conducted study, mango contains maximum amounts of phenolic acid that were 24.06 mg GAE/100 g of sample [52]. Correspondingly, Kuganesan et al. [26] found a significant amount of mango peel phenolic acids that were in range of 52.67–275.61 mg GAE/g. Different banana peel varieties have shown phenolic contents in range of 1.4593–4.63 mg GAE/100 g [53]. Pineapple peel extract determined 540–1,260 mg GAE/100 g highest phenolic acid content [54]. Papaya peel observed phenolic acid contents ranging from 1.42 to 15.18 µg GAE/µl [55]. Mallek-Ayadi et al. [56] reported that the phenolic acid content in melon peel is 332 mg/100 g by the Folin–Ciocalteu colorimeter technique. Camu-camu seeds possess 98.1 mg GAE/g phenolic acid content [57]. According to Wanlapa et al. [58], the level of phenolic acid in the peel of rambutan was 278 mg GAE/g.

2.2 Fruit pomace as phenolic acid source

Various quantities of phenolic acids have been identified in the pomace of various fruits such as raspberry, blueberry, grapes, apple, citrus, plum, kiwi fruit, peach, pear, strawberry, and various others. The grape pomace contains the maximum quantities of phenolic acids as 55.5–153.8 mg GAE/g [59]. Similarly, Younas et al. [60] found a high quantity of phenolic acid in the grape pomace as 365 mg GAE/g PWGPE. The blackberry pomace has been reported to contain 10.1 mg GAE/g phenolic acid [61]. Another study determined the maximum contents of phenolic acids in citrus pomace as 16.05 mg GAE/g DW [62]. According to Kuppusamy et al. [63], the phenolic acid in strawberry pomace was 13.8–37.5 mg GAE/g. In apple pomace, phenolic acid was articulated by various solvents and the range was observed to be 1.62–3.05 mg GAE/g powder [64].

2.3 Fruit kernel as phenolic acid source

Various studies have demonstrated a significant concentration of phenolic acid in the kernel/seed of fruits like pomegranate, avocado, mango, date palm, papaya, apple, orange, and many more. The grape seed has a high phenolic acid content as 33.9 mg GAE/g, as reported by Zhang et al. [65]. Another study shows a high concentration of phenolic acids of different grape seed varieties, ranged from 50 to 127.422 mg GAE/g [66]. Seven different apple seed varieties observed 5.74–17.44 mg GAE/g DW phenolic acid content [67]. According to Morais et al. [68], the total phenolic content in avocado was 155.30 mg GAE/100 g DW. In date seed, total phenolic contents were ranging 37.2–67 mg GAE/g [63].

3 Flavonoids

These polyphenolic compounds have two phenyl rings in their structure that are bridged up by the propane leading to the formation of 15 carbon flavan structure exhibiting (C6–C3–C6) configuration. Flavonoids are the most diverse group of polyphenols, having 12 subclasses out of which 6 are part of our diet. Up till now, different kinds of 6,000 flavonoids have been known. They occur in various parts of plants and even in their products [69]. Flavonoids can be separated into various subgroups depending on the oxidation of the C ring, the carbon of the C ring on which the B ring is bonded and the degree of unsaturation. Flavonoids in which the B ring is connected in position 3 of the C ring are referred as isoflavones. Neo flavonoids are those in which the B ring is linked in position 4; while those in which the B ring is attached in position 2 can be further split into numerous subgroups based on the structural properties of the C ring. Flavonols, flavanols, flavanones, flavones, flavanonols, or catechins, chalcones, and anthocyanins are the subgroups [70]. Flavonoids have become an essential component in a wide range of therapeutic, pharmacological, nutraceutical, and cosmetic applications. Almost all flavonoids play a role as antioxidants. The research investigated that, for protecting the body from reactive oxygen species, flavones and catechins appear to be the most potent flavonoids. Reactive oxygen species and free radicals are induced by external damage or created during normal oxygen metabolism that is constantly threatening body cells and tissues [69].

3.1 Fruit peel as flavonoid source

Substantial content of flavonoids has been found in peels of various fruits like pineapple, orange, watermelon, cantaloupe melon, banana, mango, papaya, and many more [68]. Based on the conducted research, the raw melon peel contains the maximum amounts of total flavonoids as were 204.28 mg QE 100/g DW. Similarly, Maria et al. [57] reported high levels of flavonoids in the peel of camu-camu as 550.8 µg QE/g. Significant quantities of flavonoids have been found among peel of different mango varieties and the range reported by Kuganesan et al. [26] was 140.56–187.65 mg QE/g of extract. Morais et al. [68] reported the flavonoids in apple and pomegranate peels by employing different extraction techniques with various solvents at different levels. Apple peel flavonoid contents ranged from 9.39 to 23.65 mg QE/g, while in the case of pomegranate, the reported flavonoids were 17.43–29.97 mg QE/g, as reported in the study. However, there are contradictions in the results proposed by Zulkifli et al. [71] who reported the apple peel’s flavonoids levels to be 177.86 mg QE/g. Similarly, the reported levels in pomegranate peel by Derakhshan et al. [72] range from 36 to 54 mg rutin/g.

3.2 Fruit pomace as flavonoid source

Different concentrations of flavonoids have been reported in the pomace of apple, olives, plums, grapes, and strawberries. Among pomace of different fruits, olive pomace has flavonoid contents ranging from 8.4 to 10.5 mg quercetin/g sample [63]. In apple pomace, total flavonoid contents were determined using different solvents and the levels reported were in the range of 0.54–1.85 mg RE/g powder [64]. The richest source of flavonoids was the grape pomace. The results of Xu et al. [59] demonstrated that total flavonoids in pomace of four different varieties of grapes ranged from 32.8 to 91.7 mg CE/g extract, but the results of the de Oliveira et al. [73] study show a contradiction as it reports TFC ranging from 1822.07 to 3629.19 mg CE/g, respectively.

3.3 Fruit kernel as flavonoid source

Various studies show significant concentration of flavonoids in the seeds/kernels of dates, mango, avocado, apricot, camu-camu, passion fruit, and several others. Apricot kernel showed the highest concentration of flavonoids ranging from 226.18 to 509.34 μg rutin equivalent/g dry extract [74]. Kuganesan et al. [26] reported total flavonoids in mango seed kernel in the range of 98.34–110.11 mg QE/g of extract. According to Maria et al. [57], flavonoid contents found in the seeds of camu-camu were 49.6 µg QE/g that were very low compared to the peel. According to Morias et al. [68] the total flavonoids contents in avocado seed were 30.02 mg QE 100/g DW, but Oboh et al. [75] reported that the seed extract contains 19.45 mg QE/g of flavonoids.

4 Tannins

Tannins are the heterogeneous group of polyphenols that are soluble in water, possess high molecular weight 500–3,000 Da, with numerous hydroxyl groups around 20, and impart astringent taste to the product in which they are present. Complex tannins, ellagitannins, Gallo tannins, and condensed tannins are the four types of tannins classified according to their structural features [76].

The two main categories of tannins are hydrolyzable tannins and condensed tannins, which themselves have several subgroups. Above 8,000, tannins have been identified [77,78,79]. Tannins have several positive pharmacological actions, including anti-inflammatory, antioxidant, antidiabetic, anticancer, and cardioprotective properties, despite their limited bioavailability [80].

4.1 Fruits skin as tannin source

Tannins are widely distributed in the skins/peels of various fruits, including apple, banana, mango, orange, kiwi, watermelon, and several others. Naguib et al. [49] conducted research on several fruit peels and reported high contents of tannins in the peel of banana that were 24.45 μg/g dry weight. Almost similar results for tannins were reported in banana peel by Aboul-Enein et al. [81] that fall in the range of 14.69–24.21 mg TE/g DW. Kanatt et al. [82] reported tannins in mango peels of four varieties by using different solvents and extraction techniques and contents ranged from 1.01 to 84.91 mg CE/g; however, total tannin contents in two cultivars of mango peel as per reported by Peng et al. [83] were in the range of 6.90–8.52 mg CE/g. Mwagandi Chimbevo et al. [84] did not detected any type of tannins in the peels of Annona squamosa and Annona muricata. Reported levels of tannins in kiwi peel by Salama et al. [85] and Naguib et al. [49] were in between 10.78 and 16.76 mg TE/g DW and 3.921 μg/g DW, respectively. Orange and watermelon peels showed lower levels of tannins that were 0.1520 and 0.0664 g GAE/mg of extract [86].

4.2 Tannins in pomace of various fruits

Contents of tannins are also found in the pomace of various fruits like apple, orange, sweet lemon, pineapple, apricot, and others. Nagarajaiah and Prakash [87] articulated that tannin content in pomace of four different fruits including sweet lemon, blue grapes, pineapple, and orange. Among these fruits, higher concentrations were observed in blue grapes that were 2,391 mg TAE/100 g and pineapple pomace found to have lower contents that were 392 mg TAE/100 g. Cheaib et al. [36] reported tannins in orange pomace to be 2.5 mg/l. Kara et al. [88] tested tannin contents in pomace of apple and pomegranate and reported that total condensed tannins in both the pomace were 4.40 and 5.50 mg CatE/g, DM. Cheaib et al. [89] use two different extraction techniques for the tannins’ recovery from apricot pomace and reported the tannin level as 1.1–3.6 mg/l.

4.3 Fruit kernels as tannin source

Seeds of various fruits have proven to be a good source of tannins, especially watermelon, black plums, tamarind, guava, apple, etc. Arshad et al. [90] reported tannin contents in various fruit seeds and among these black plum seeds exhibited high contents that were 191.25 mg/g dry seeds followed by tamarind, guava, apple, and watermelon. The tannin contents of these were 129.5, 1.25, 0.205, and 0.11 mg/g dry seeds, respectively. Cvetanović et al. [91] reported minimum and maximum values of tannins contained in tamarind seeds by utilizing different solvent concentrations. The minimum value reported was 89.12 mg CE/g and the maximum value was 282. 47 mg CE/g. Chai et al. [92] reported tannins in the seeds of 11 different varieties of rambutan and the minimum and maximum contents that they found were 4.40 and 26.68 mg CE/100 g of sample.

5 Coumarins

Coumarins belong to the benzopyrone family commonly found in many medicinal plants [93]. Coumarins are fused benzene and α-pyron ring that represents a significant low-molecular phenol group [94]. Coumarins are secondary metabolites, found in a wide variety of higher plants, but also detected in some microorganisms and animal species [95]. Natural coumarins are divided into different classes on the basis of their chemical enormous diversity, such as simple coumarins, isocoumarins, furanocoumarins, and pyranocoumarins [96]. The coumarins are of great interest due to their pharmacological properties. In particular, their physiological, bacteriostatic, and anti-tumor activities make these compounds attractive backbone derivatization and screening as novel therapeutic agents [97].

A total of 800 coumarin-derived compounds have been naturally distinguished from approximately 600 genera in 100 families [98].

5.1 Fruit peels as coumarin source

High contents of coumarins have been found in the peel of different fruits like pomegranate, banana, orange, mango, pear, and many others. Dugrand et al. [99] analyzed citrus peel extracts from six different varieties and reported cumarins as 0.77–102.43 mg/kg. Mercolini et al. [100] reported that the level of coumarins in different varieties of citrus such as grape fruit, sweet orange, bitter orange, lemon, and lime ranged 1–18, 0.1–3.3, 14–441, 0.1–0.3 and 35–331 µg/g, respectively. Masuda et al. [101] in extracts from various varieties of citrus peel the coumarins concentration was reported to be 1.273–308.125 (µg/g). In extracts from various varieties of citrus peel coumarins, the concentration was 1.273–308.125 µg/g [102]. Pear peel observed coumarin concentration 49.316 µg/g [103]. The banana peel acetone extract contained 0.79 mg/100 g coumarin contents [81]. The peel of mango has 24.696 µg/g coumarin contents [103]. The coumarin content in pomegranate peel was 0.41 mg/100 g [104]. In other study, the highest coumarin content in pomegranate peel was 293.77 mg/100 g [103]. Correspondingly, the peel pomegranate by ethanol extracts found 5.37 mg/100 g DW coumarin contents [105].

5.2 Fruit pomace as coumarin source

Coumarin contents have found in various fruit pomace like olive, grape, citrus, guava, and many others. The identification of coumarins contents in pomace olive by the methanolic extraction method was 0.169–0.232 mg/g ddp as reported by Khairy et al. [106]. The varieties of grape pomace contained 0.23–0.66 mg/kg fw coumarin contents in a study by Pintać et al. [107]. Multari et al. [108] analyzed citrus pomace and reported the coumarin contents as 0.62 mg/kg. Ribeiro da Silva et al. [109] reported 102 mg/100 g coumarin contents in guava pomace. Correspondingly, Mota et al. [110] in their study on guava pomace ethanolic extraction reported 0.78 mg/100 g coumarin quantity.

5.3 Fruit seeds as coumarin source

Excess amount of coumarins has found in many fruit seed like citrus, pomegranate, and many more. Mercolini et al. [100] reported that the coumarin contents in different orange seeds ranged from 12 to 980 µg/g. Russo et al. [111] found 5.9 mg/kg coumarin contents in the citrus seed. Morais et al. [109] reported 60.28 mg/100 g DW coumarins in the passion fruit. The maximum concentration of coumarins in pomegranate seed was 1.99–6.53 µg/g as reported by Mandal et al. [61]. Yang et al. [112] reported 0.02% coumarin contents in Mammea americana seed.

6 Stilbenes and its different fruit waste sources

Stilbenes are a small family of plant secondary metabolites derived from the phenylpropanoid pathway and produced in a number of unrelated plant species [113]. Although their molecular backbone consists only of 1,2-diphenylethylene units, stilbenes show an enormous diversity with regard to the different units present, the degree of polymerization, and the pattern of oligomer construction. In plants that naturally produce stilbenes, these metabolites are generally accumulated in both free and glycosylated forms. Glycosylation of stilbenes could be involved in their storage, transport from cytoplasm to apoplasm, and protection from peroxidative degradation [114]. Stilbenes are a small family of plant secondary metabolites derived from the phenylpropane pathway and produced in many unrelated plant species [113]. Although their molecular backbones consist of only 1,2-diphenylethylene units, stilbenes show huge differences in the different units present, degree of polymerization, and oligomeric structural patterns. In plants that naturally produce stilbene, these metabolites typically accumulate in free and glycosylated forms. Glycosylation of stilbenes may be involved in their storage, transport from the cytoplasm to the apoplast, and protection from peroxidative degradation [114].

Genetic modification of tomato plants results in the accumulation of different levels of four stilbene species (i.e., trans and cis-resveratrol and trans and cis-resveratrol) in their fruits, depending on the stage of ripening. Stilbenes preferentially accumulate in the peel in glycosylated form, both in immature and mature stages. The highest amounts of trans-resveratrol and trans-resveratrol were found in the peels of fruits harvested at maturity [115].

By-products from the food industry, such as passion fruit seeds, have increased significantly due to their added value due to their properties such as potential antioxidant activity. The purpose of this study was to determine the presence of paclitaxel and resveratrol in various extracts of passion fruit (Passiflora edulis) seeds from Madeira, using commercial passion fruit oil as a reference. Commercial oils and extracts obtained by the traditional Soxhlet method with ethanol and acetone do not show the presence of two stilbenes, paclitaxel and resveratrol [115].

7 Mechanism of polyphenols in type 2 diabetes management

Type 2 diabetes mellitus is described as a condition in which the insulin produced by the pancreatic β cells faces resistances from the insulin receptors that are embedded in the bodily cells due to the deposition of fatty deposits in respective receptors. As a result of this, at initial stages, the levels of insulin are high in the blood, but later the levels drop as the β cells become defective [116]. Presently, polyphenol-based drugs’ utilization for the treatment of diabetes and other complex disorders has been increased due to their biological functions. Various studies have emphasized that intake of polyphenols in the diet especially phenolic, flavonoids, tannins, and coumarins has an association with the reduction in the prevalence of type 2 diabetes mellitus [117,118]. The hypoglycemic effects of polyphenols are primarily attributable to reduced intestinal absorption of dietary carbohydrates and regulation of the enzymes involved in glucose metabolism, enhancing glucose metabolism, β-cell function, and insulin action, insulin stimulation, and insulin secretion antioxidant and anti-inflammatory effects of components. The suppression of α-glucosidase and α-amylase, the major enzymes responsible for the digestion of dietary carbohydrates to glucose, is one of the most well-known effects of polyphenols on carbohydrate metabolism. Some polyphenols, including catechins and epicatechins from green tea, chlorogenic acids, ferulic acids, caffeic and tannic acids, quercetin, and naringenin, may inhibit Na+-dependent glucose transporters SGLT1 and SGLT2 to decrease glucose absorption from the intestine. Several studies have demonstrated that polyphenolic substances can also modulate postprandial glycemia and prevent the onset of glucose intolerance via a facilitated insulin response and decreased production of glucose-dependent insulinotropic polypeptide and glucagon-like polypeptide-1 [31,119]. Natural fruits with high polyphenol content, such as blackberries, red grapes, and apricots, can regulate carbohydrate metabolism through a variety of methods, including maintaining and repairing beta-cell function and improving insulin releasing activity and cellular glucose absorption [120]. A previous study shows that polyphenols found in food items like coffee, cocoa, propolis, guava tea, grape seeds, whortleberry, and red wine have been found to have anti-diabetic characteristics by increasing glucose metabolism and reducing insulin resistance, vascular function, and HbA1c levels in T2D patients [29]. Polyphenols reduce hyperglycemia and increase insulin sensitivity and acute insulin secretion. Some of the mechanisms that could be involved: insulin secretion stimulation, inhibition of carbohydrate digestion, glucose uptake in insulin-sensitive tissues, modulation of glucose release from the liver, modulation of intracellular signaling pathways, activation of insulin receptors, and gene expression [28]. Protection of pancreatic cells from glucose toxicity, antioxidant properties, anti-inflammatory properties, inhibition of amylases or glucosidases, decreased starch digestion, and prevention of advanced glycation end products generation is all advantages of dietary polyphenols for T2D [121]. Glycation of proteins is thought to have a major role in diabetes complications and illnesses. Cao et al. [29] analyzed the effects of glycation on serum albumin (HSA) function. The ligand-binding properties change when HSA is glycated. It is suggested that glycation reduces its affinity for acidic drugs like “polyphenols and phenolic acids.” These non-enzymatic alterations have far-reaching implications for metabolism and regulation, and they may be to responsible for the problems in diabetes infection rates [122]. Gao et al. [123] reported that polyphenols suppress the risk of diabetics complication through a variety of ways. They do so by either inhibiting the absorption of glucose in the GI tract or activating the insulin receptors in the cells. Chukwum and colleagues [124] reported that polyphenols reduce the carbohydrate digestion and increase the uptake of glucose being stored in the liver. Similarly, Ramya et al. [125] provided evidence that the polyphenols inhibit the α-amylase and α-glucosidase activity, thus suppressing the level of glucose in blood plasma. Niederberger and coworkers [126] reported that the polyphenol phloridzin has the ability to inhibit the activity of SGLT 1 a glucose transporter present in the small intestine, thus minimizing the uptake of glucose from the intestine into the blood. Moloto et al. [127] in their study demonstrated that the structure of polyphenols plays an important role in the inhibition of carbohydrate digesting enzymes particularly α-amylase and β-glucosidase. The OH group of these polyphenols forms connection with the active sites of enzyme and thus hinders their capacity to hydrolyze the carbohydrates. Tables 1 and 2 show various in vitro and in vivo studies.

Table 1

Polyphenols in diabetes management – in vitro studies

Waste type Subjects Polyphenols IC50 exhibited by polyphenol used Standard drug IC50 of standard drug Extracts exhibiting maximum enzymatic inhibitory action Mechanism of action References
Punica granatum L. fruit peel Hepatocytes Ferulic acid 0.0106 mg/ml Acarbose 0.0192 mg/ml Acetone Polyphenols reduces the carbohydrate digestion and increases the uptake of glucose being stored in the liver [124]
Seeds from various Phoenix dactylifera L. cultivars α-Glucosidase from Saccharomyces cerevisiae Ferulic acid 0.01031–0.01354 mg/ml Acarbose 0.36938 mg/ml Aqueous N/R [128]
Pomegranate peel α-Glucosidase from baker’s yeast type I Gallic and Ellagic acid 0.00209 mg/ml Acarbose 0.242 mg/ml Ethanol N/R [84]
α-Amylase from porcine pancreas 0.1229 mg/ml 0.00552 mg/ml
Grape seed α-Glucosidase from baker’s yeast Polyphenols 0.02525 mg/ml Acarbose 1.25624 mg/ml Aqueous N/R [129]
α-Amylase 0.06668 mg/ml 0.11417 mg/ml
Pouteria torta epicarp α-Amylase from porcine pancreas Phenolics 0.009 mg/ml Acarbose 0.0063 mg/ml Hydro acetone The level of glucose in blood is reduced by the respective polyphenol through the reduction in the absorption of glucose from the intestine [130]
Jackfruit peel α-Glucosidase (from yeast) Phenolics 0.05 mg DM/ml Acarbose 0.59 mg DM/ml Methanol N/R [65]
Korkobbi seeds Intestinal α-glucosidase Phenolics, flavonoids, tannins 0.353 mg/ml Acarbose 0.161 mg/ml Aqueous These polyphenols make connections with the active sites of the carbohydrate hydrolyzing enzymes that in turns extend the duration for carbohydrate digestions, reduces glucose retention and ultimately prevents the rise in levels of glucose in blood plasma [131]
Pancreatic α-amylase 0.783 mg/ml 0.232 mg/ml
Arechti seeds Intestinal α-glucosidase Phenolics, flavonoids, tannins 0.768 mg/ml Acarbose 0.161 mg/ml Aqueous
Pancreatic α-amylase 0.987 mg/ml 0.232 mg/ml
Chaenomeles speciosa peel α-Glucosidase Chlorogenic acid and ferulic acid 2.66 mg/ml N/R N/R Methanol N/R [132]
Pomegranate peel α-Glucosidase from (Intestinal mucosa) Phenols and flavonoids 0.28521 mg/ml Acarbose 0.205 mg/ml Ethyl acetate N/R [133]
Pear peel α-Glucosidase from Saccharomyces cerevisiae Chlorogenic acid, vanillic acid, ferulic acid, and rutin 0.19 mg/ml N/R N/R Methanol/water Binding of polyphenols with the active sites of α-glucosidase inhibits the working capability of respective enzyme thus preventing hyperglycemia [134]
Table 2

Polyphenols in diabetes management – in vivo studies

Reference Waste type Polyphenols Subject Drug Inducing diabetes Quantity of drug inducing diabetes Duration of treatment Quantity of dose that inhibited the diabetic activity Extract used Standard drug Level of standard drug reducing the glucose Amount of polyphenol reducing the level of glucose Mechanism of action
[125] Punica granatum peel Phenolics, flavonoids, alkaloids, terpenoids Albino Wister male and female rats Alloxan monohydrate 150 mg/kg 28 days 500 mg/kg BW Methanol Glibenclamide 44% 39% The polyphenols inhibit the α-amylase and α- glucosidase activity so reducing the level of glucose in blood plasma
Citrus aurantifolia peel Phenolics, carotenoid, flavonoids, terpenoids Albino Wister male and female rats Alloxan monohydrate 150 mg/kg 28 days 500 mg/kg BW Methanol Glibenclamide 42% 41%
[135] Pomegranate peel Phenolics, flavonoids Albino Wister rats Alloxan monohydrate 100 mg/kg 56 days 200 mg/kg Hydro-methanol Glibenclamide 121 mg/dl 101.6 mg/dl N/R
[136] Punica granatum L. peel Phenolics, tannins Male guinea pigs Streptozotocin 150 mg/kg 4 weeks 500 mg/kg Methanol N/R N/R 65.70% N/R
[133] Pomegranate peel Phenols, flavonoids C. elegans N/R N/R 25 days 500 mg/kg Ethyl acetate Acarbose N/R N/R N/R
[137] Citrus sinensis peel Flavonoids Albino Wister rats Alloxan monohydrate 150 mg/kg 15 days 500 mg/kg BW Mixture of ethanol and acetone Glibenclamide 42.76% 61% The polyphenols inhibit the α-amylase enzyme activity which is responsible for breakdown of carbohydrate into glucose thus prevent the glucose level in blood
[138] Punica granatum peel Flavonoids, tannins Male Wister albino rat Steptozotocin 40 mg/kg 28 days 100 mg/kg N/R Glibenclamide 211.17 mg/dl 130.33 mg/dl N/R
[137] Mangifera indica kernel Flavonoids, phenolic acid Adult male Wistar rats Steptozotocin 40 mg/kg BW 21 days 20% Methanol Metformin 64.95% 61.67% The polyphenol inhibit the α-amylase and α- glucosidase activity thus decrease in intestinal absorption of carbohydrate
[139] Punica granatum peel Phenolics, tannins Male Swiss albino rats Steptozotocin 50 mg/kg 21 days 200 mg/kg Aqueous Insulin N/R N/R The polyphenol inhibit the beta glucosidase and has an effect on GLUT4 function
[134] Pear peel Phenolic acids, flavonoids, terpenes Kunming mice Steptozotocin 100 mg/kg 3 weeks 500 mg/kg Methanol/water N/R N/R 32.96 mg/l The polyphenol binds with the active site of carbohydrate hydrolyzing enzyme such as β-glucoside thus delay the carbohydrate metabolism and prevent the glucose level in blood
[140] Mango peel Phenolic acids, flavonoids Male Wistar rats Steptozotocin 45 mg/kg BW 16 weeks 50 mg/kg Acetone N/R N/R 4500 mg/day N/R

8 Conclusions

The present review summarizes that waste generated during the processing of fruits contains ample quantities of polyphenols in it. The major polyphenols that are present in the wasted portion of fruits (seeds, peel, and pomace) mainly include the phenolic acids, flavonoids, and tannins. Polyphenols are an important class of phytochemicals and offer various benefits to humans upon consumption. One of the major benefits of these polyphenols may be their capability to cure various degenerative diseases, and diabetes is one among them. From clear investigation, it was found that polyphenols show a positive effect in the management of diabetes, particularly the type 2. It is suggested that instead of discarding the inedible components of fruits proper extraction procedures must be utilized for the recovery of these polyphenols from the fruit wastes so that beneficial products can be made out of them and treatment of various ailments including diabetes can be facilitated by using these bioactive commodities. Besides this such practices would also minimize the harmful impact of wastes on the environment. It is therefore advisable to utilize waste-derived polyphenols from the fruits for the recovery of these functionally essential constituents so that they can be used in various formulations for the treatment and cure of diabetes and other disorders as they are considered to be far better than the synthetic products because they provide more benefits and fewer harms.



cardiovascular diseases


gallic acid equivalent


dry weight


purified white grape pomace extract


milligram per gram


milligram per Liter


milligram per Kilogram


quercetin Equivalent




rutin equivalent


catechin equivalent


tannic acid equivalent


tannic acid equivalent


catechin equivalent


dry matter


dried defatted pomace

  1. Funding information: No funding was received.

  2. Author contributions: All authors took an active part in the collection, processing, and description of the presented literature data

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Ethics approval: The conducted research is not related to either human or animal use.

  5. Consent to participate: Not applicable.

  6. Consent for publication: Not applicable.

  7. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.


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Received: 2022-09-30
Revised: 2022-11-18
Accepted: 2022-12-21
Published Online: 2023-01-10

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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