Fruit Peels: Food Waste as a Valuable Source of Bioactive Natural Products for Drug Discovery

Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications.


Introduction
Approximately 89 million tons of food waste is produced in the European Union, and this figure is anticipated to increase by a factor of 40 in the future [1]. Fruits and vegetables are considered to be basically used food products being either fully cooked, nominally cooked or uncooked [1]. It has been found that the processing of vegetables and fruits alone produces a notable waste of 25-30% of the total product. Furthermore, peels, pomace, rind and seeds are considered to be among the most common wastes. In spite of this, material contains valuable biologically active molecules including enzymes, carotenoids, oils, polyphenols and vitamins. In point of fact, these bioactive molecules demonstrated their significant industrial application including as a food to generate edible films along with probiotics and other industrial applications to develop value-added products [1].
It has been reported that large amounts of secondary metabolites are present in fruit and vegetable wastes and these waste materials have been studied for phenolic molecules, dietary fibers and other biologically active metabolites by extraction [1,2]. Scientific investigations revealed that phytochemicals and essential nutrients are largely present in the peels, seeds, fruits and vegetables [1]. For example, the skin of grapes, avocados, lemons along with seeds of mangoes and jackfruits comprise up to a 15% larger phenolic content than fruit pulp [3,4]. The fruit and vegetable wastes could thus be employed to obtain biologically active metabolites that could be utilized in food industries, cosmetics, food, pharmaceutical and textile industries. The proper utilization of fruit peels will not only resolve the large number of environmental problems, but this strategy will improve health through enriched food products comprising health-enhancing molecules. To the best of our knowledge no comprehensive review has been published about natural products which were isolated from fruit peels and our review mainly focus on the natural products which are purely isolated and their biological effects but not detected via mass techniques. Indeed, some minireviews have been published about the fruit peel crude extracts and biological activities or invidual reviews of fruit peels and their natural products [1,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]].

Traditional Uses of Fruit Peels
Citrus (C) peels are not fully utilized and these waste materials contain highly valuable bioactive molecules [20]. In addition, fruits and their peels are folklorically used to treat cough, digestive problems, infection, muscle pain and skin inflammation [21,22]. These folkloric preparations are formulated from the peel, fruit and flowers [23]. Notably, peels of C. reticulata and C. unshiu are used under the trade name "Chimpi" in Japan as crude drugs. Similarly, C. aurantium dried peels are employed as the popular folkloric drug "Touhi." [20,24]. The "tangerine", a citrus fruit, is considered as one of the most popular foods in many countries around the world. Citrus peel, named "Chenpi" in China, has been employed as a medicine to treat gastrointestinal and respiratory diseases. In addition, the peel of a tangerine is used in drinks and baking in Western countries as an aromatic spice [25][26][27]. Citrus fruit peels are reported to be used in Chinese medicine to treat muscle pain, stomachache, cough, skin inflammation and high blood pressure [28]. Wampee (Clausena lansium) peels are used to treat bronchitis and stomachache in China and Indian folk medicine [29]. The fruit peels of wampee (Clausena lansium) are reported to be utilized for stomachic, bronchitis and as a vermifuge [29] while fruit peels of Jaboticaba (Plinia peruviana) are employed for diarrhea, skin irritation, hemoptysis and asthma [30].

Sesquiterpenes
Elaeagnus rhamnoides was reported to contain nor-sesquiterpene 39 ( Figure 5) from its fruit peel and its absolute configuration was measured via the TDDFT-ECD method. In antiviral screening, compound 39 was found to cause a 2 log10 reduction in HSV-2 yield and additionally possesses antiviral effects as determined in the qPCR method [39]. A new sesquiterpene glycoside 40 was found to be produced by the fruit peels of C. limon [44]. Spathulenol (41) was isolated from the peels of Annona squamosal [45] while crytomeriodiol (42) was produced by peels of Goniothalamus scortechinii [41].

Sesquiterpenes
Elaeagnus rhamnoides was reported to contain nor-sesquiterpene 39 ( Figure 5) from its fruit peel and its absolute configuration was measured via the TDDFT-ECD method. In antiviral screening, compound 39 was found to cause a 2 log 10 reduction in HSV-2 yield and additionally possesses antiviral effects as determined in the qPCR method [39]. A new sesquiterpene glycoside 40 was found to be produced by the fruit peels of C. limon [44]. Spathulenol (41) was isolated from the peels of Annona squamosal [45] while crytomeriodiol (42) was produced by peels of Goniothalamus scortechinii [41].

Sesquiterpenes
Elaeagnus rhamnoides was reported to contain nor-sesquiterpene 39 ( Figure 5) from its fruit peel and its absolute configuration was measured via the TDDFT-ECD method. In antiviral screening, compound 39 was found to cause a 2 log10 reduction in HSV-2 yield and additionally possesses antiviral effects as determined in the qPCR method [39]. A new sesquiterpene glycoside 40 was found to be produced by the fruit peels of C. limon [44]. Spathulenol (41) was isolated from the peels of Annona squamosal [45] while crytomeriodiol (42) was produced by peels of Goniothalamus scortechinii [41].

Alkaloids
Caulilexin C (47) (Figure 7) was reported from the peel of Elaeagnus rhamnoides and this metabolite is included in the family of the phytoanticipins. Indol glucosinolates are the biosynthetic precursors of caulilexins [39]. Previously, this compound was reported from the cauliflower [48] as well as from Brassica rapa [49]. In another report, the pyrrolizine alkaloid named punicagranine (48) was reported from the peels of Punica granatum (pomegranate) and its structure was confirmed through an X-ray analysis. Punicagranine (48) is a very unusual pyrrolizine-type alkaloid featuring both a furan-2-carbonyl and carboxylic acid. Biosynthetically, this metabolite may be considered to be constructed through the condensation of the pyrrolizine alkaloid and 2-furoic acid. In a biological assay, punicagranine (48) exerted anti-inflammatory effects with an IC50 of 22.8 μM while the same compound did not show cytotoxicity towards RAW 264.7 cells [50].
Justino et al. [51] demonstrated that the polyphenol-enriched fraction of the fruit peel of Annona crassiflora illustrated promising antioxidant effects and these fractions can be employed in clinical applications to treat diabetes complications. Further study indicated that ca. 15 mg kg −1 day −1 could be considered to be an initial dose to undertake all important human studies. Stephalagine (49) was isolated from the fruit peel of A. crassiflora. The EtOH extract of A. crassiflora peels inhibited pancreatic lipase (PL) with IC50: 104.5 µ g/mL and notably the stephalagine showed higher PL inhibition with IC50: 8.35 µ g/mL [52]. In addition, this alkaloid exerted significant antinociceptive effects in vivo [53].

Alkaloids
Caulilexin C (47) (Figure 7) was reported from the peel of Elaeagnus rhamnoides and this metabolite is included in the family of the phytoanticipins. Indol glucosinolates are the biosynthetic precursors of caulilexins [39]. Previously, this compound was reported from the cauliflower [48] as well as from Brassica rapa [49]. In another report, the pyrrolizine alkaloid named punicagranine (48) was reported from the peels of Punica granatum (pomegranate) and its structure was confirmed through an X-ray analysis. Punicagranine (48) is a very unusual pyrrolizine-type alkaloid featuring both a furan-2-carbonyl and carboxylic acid. Biosynthetically, this metabolite may be considered to be constructed through the condensation of the pyrrolizine alkaloid and 2-furoic acid. In a biological assay, punicagranine (48) exerted anti-inflammatory effects with an IC 50 of 22.8 µM while the same compound did not show cytotoxicity towards RAW 264.7 cells [50]. Steroidal alkaloids named solasodine (50), solamargine (51) and solasonine (52) (Figure 8) were isolated from the fruit peels of Solanum melongena. Alkaloids 50-52 exerted cytotoxic effects towards HCT116 (colon cancer), HEPG2 (liver cancer), HEP2 (larynx cancer), HELA (cervix cancer) and MCF7 (breast cancer), with IC50 values ranging from 2.1 to 9.0 µ M [54]. Further study revealed that alkaloids 50-52 induced potent cytotoxic effects Justino et al. [51] demonstrated that the polyphenol-enriched fraction of the fruit peel of Annona crassiflora illustrated promising antioxidant effects and these fractions can be employed in clinical applications to treat diabetes complications. Further study indicated that ca. 15 mg kg −1 day −1 could be considered to be an initial dose to undertake all important human studies. Stephalagine (49) was isolated from the fruit peel of A. crassiflora. The EtOH extract of A. crassiflora peels inhibited pancreatic lipase (PL) with IC 50 : 104.5 µg/mL and notably the stephalagine showed higher PL inhibition with IC 50 : 8.35 µg/mL [52]. In addition, this alkaloid exerted significant antinociceptive effects in vivo [53].

Flavones, Flavanone and Condensed Tannins
Benzoyltyramines, atalantums H-K (76-79) along with atalantums D-G (67-70) and 80 were reported form the fruit peels of Atalantia monophylla. Biological studies showed that molecules 67 and 68 exerted cytotoxic effects towards cervical (HeLa), breast (MCF-7) and colon (HCT116) cancer with IC 50s : ranging from 16-25 and 15-18 µg/mL, respectively. On the other hand, benzoyltyramine 69 was slightly more active than compound 67 (IC 50s : ranging from 16-25 µg/mL), whereas compound 70 was slightly less active with IC 50s : ranging from 20-35 µg/mL [60].  Hesperidin (94) ( Figure 12) is largely present in citrus species such as Citrus sinensis (sweet orange peel) and tangerine (C. reticulata) [62,63]. In addition, hesperidin (94) and naringin are present in orange juice and these natural products are reported to be present in human plasma after diets involving grapefruit and orange as food sources. Hesperidin (94) exerted potential anti-inflammatory, anticarcinogenic, antimicrobial and antioxidant effects [63] and has additionally been successfully employed as a supplemental dietary agent since it has been found that a deficiency thereof causes weakness, aches and night leg cramps. Supplemental hesperidin has been used to treat excess swelling of the legs and oedema [63].

Flavones, Flavanone and Condensed Tannins
Hesperidin (94) along with the polymethoxy flavones 95-98 were isolated from the fruit peels of Citrus 'Hebesu' and tested for their biological effects. Flavones 96-98 exerted potent anti-neuroinflammatory effects through the inhibition of the expression of IL-1β mRNA [20]. Notably, polymethoxyflavonoids (PMFs) are found to be largely present in citrus plants. It is thus not surprising that citrus peels are one of the richest sources of PMFs including C. sinensis (sweet orange) and C. reticulata (mandarin) [64]. PMFs have demonstrated a plethora of biological effects viz., anticancer, antioxidative, antiviral and anti-inflammatory effects [64][65][66][67].
Tangeretin (95), in anti-arenaviral screening, demonstrated a reduction (65%) in pseudotype infectivity with EC50: 6.0 µ M [53]. LASV-GP/HIV-luc infectivity was also decreased by tangeretin (95)   Hesperidin (94) (Figure 12) is largely present in citrus species such as Citrus sinensis (sweet orange peel) and tangerine (C. reticulata) [62,63]. In addition, hesperidin (94) and naringin are present in orange juice and these natural products are reported to be present in human plasma after diets involving grapefruit and orange as food sources. Hesperidin (94) exerted potential anti-inflammatory, anticarcinogenic, antimicrobial and antioxidant effects [63] and has additionally been successfully employed as a supplemental dietary agent since it has been found that a deficiency thereof causes weakness, aches and night leg cramps. Supplemental hesperidin has been used to treat excess swelling of the legs and oedema [63].
Hesperidin (94) along with the polymethoxy flavones 95-98 were isolated from the fruit peels of Citrus 'Hebesu' and tested for their biological effects. Flavones 96-98 exerted potent anti-neuroinflammatory effects through the inhibition of the expression of IL-1β mRNA [20]. Notably, polymethoxyflavonoids (PMFs) are found to be largely present in citrus plants. It is thus not surprising that citrus peels are one of the richest sources of PMFs including C. sinensis (sweet orange) and C. reticulata (mandarin) [64]. PMFs have demonstrated a plethora of biological effects viz., anticancer, antioxidative, antiviral and anti-inflammatory effects [64][65][66][67].
Zhang et al. [62] demonstrated in vivo studies on the protective effects of flavone 98 in the mediation of cardiac hypertrophy in which it was demonstrated to inhibit aortic banding (AB)-induced cardiac hypertrophy, as measured by cardiomyocytes cross-sectional area, cardiac weight-to-body weight ratio, cardiac function and through gene expression of markers of hypertrophy. The 98 supplementation in cardiac hypertrophy inhibited NOX4 and NAPDH oxidase (NOX)2 expression and alleviated myocyte apoptosis and endoplasmic reticulum (ER) stress. Further studies suggested that the administration of flavone 98 decreased cardiomyocyte hypertrophic response in neonatal rat as stimulated through phenylephrine (PE) and decreased ER stress. However, this study indicated that 98 significantly reduced NOX2 expression but did not affect NOX4 expression in vitro. The authors suggested that the inhibition of oxidative and ER stress by flavone 98 in the cardiac muscle may indicate an effective therapy for the management of cardiac hypertrophy [77].
Zhang et al. [62] demonstrated in vivo studies on the protective effects of flavone 98 in the mediation of cardiac hypertrophy in which it was demonstrated to inhibit aortic banding (AB)-induced cardiac hypertrophy, as measured by cardiomyocytes cross-sectional area, cardiac weight-to-body weight ratio, cardiac function and through gene expression of markers of hypertrophy. The 98 supplementation in cardiac hypertrophy inhibited NOX4 and NAPDH oxidase (NOX)2 expression and alleviated myocyte apoptosis and endoplasmic reticulum (ER) stress. Further studies suggested that the administration of flavone 98 decreased cardiomyocyte hypertrophic response in neonatal rat as stimulated through phenylephrine (PE) and decreased ER stress. However, this study indicated that 98 significantly reduced NOX2 expression but did not affect NOX4 expression in vitro. The authors suggested that the inhibition of oxidative and ER stress by flavone 98 in the cardiac muscle may indicate an effective therapy for the management of cardiac hypertrophy [77].
Nobiletin (98) has additionally been reported to possess potential anti-tumor and antiinflammatory potential [78,79]. In addition, this flavone has been reported to inhibit NF-κB activation mediated by LPS in macrophages in mice [80]. However, it is still unknown how nobiletin (98) prevents the activation of NF-κB. It is however known that it reduces the activation of NF-κB by inhibiting its DNA-binding potential. In addition, flavone 98 blunted NF-κB transactivation and DNA-binding capacity of p50/p65 and was mediated by LPS [78]. Additional results demonstrated that it neither altered LPS-mediated phosphorylation and IκBα degradation, nor the NF-κB translocation to the nucleus. These findings, therefore, show that the inhibitory action of nobiletin (98) on proinflammatory mediator's expression may involve the inhibition of NF-κB activity [78].

Hydrolyzable Tannins
Punicalagin (156) (Figure 18) was isolated from the peel of the pomegranate and exerted antifungal effects towards Trichophyton rubrum with an MIC of 62.5 μg/mL, whereas the same compound was cytotoxic on Vero cell (90%) [103]. Punicalagin (156), punicalin (157) and ellagic acid (158) were isolated from pomegranate fruit peels. Tannins 156-158 prevent protease-mediated effects in vitro through acting on HCV NS3/4A protease directly (with IC50: < 0.1 µ M for tannins 156 and 157 and compound 158 has IC50: 1.0 µ M). Notably, these compounds are all reported to be associated with no toxic effects side effects ex vivo and were quite safe at 5000 mg/kg when given acutely in BALB/c mice. Pharmacokinetics data indicated that compounds 156-158 are readily bioavailable [104].
Literature revealed that tannins can form complexes with metal ions as well as target macromolecular polysaccharides and proteins [105]. Hence, these compounds may interact with enzymes through their interaction with any zinc moiety thus preventing its activity. In addition, some studies have significantly proven their selective binding of PGN, PLN and EA to NS3 protease enzymes at their substrate binding sites and this is further supported by molecular docking studies [23,104]. It is noted that molecules 156 and 157 possess galloyl residues that provide further evidence for their inhibitory effects against NS3/4A protease.
Further study revealed that compounds 156-158 demonstrated biological effects towards RNA replication of HCV and the exact mechanism of this activity is yet to be investigated. Since compounds 156-158 inhibit NS3 protease, thus affecting HCV polyprotein proteolytic processing which in turn leads to a decreased active viral RNA-dependent

Hydrolyzable Tannins
Punicalagin (156) (Figure 18) was isolated from the peel of the pomegranate and exerted antifungal effects towards Trichophyton rubrum with an MIC of 62.5 µg/mL, whereas the same compound was cytotoxic on Vero cell (90%) [103]. Punicalagin (156), punicalin (157) and ellagic acid (158) were isolated from pomegranate fruit peels. Tannins 156-158 prevent protease-mediated effects in vitro through acting on HCV NS3/4A protease directly (with IC 50 : < 0.1 µM for tannins 156 and 157 and compound 158 has IC 50 : 1.0 µM). Notably, these compounds are all reported to be associated with no toxic effects side effects ex vivo and were quite safe at 5000 mg/kg when given acutely in BALB/c mice. Pharmacokinetics data indicated that compounds 156-158 are readily bioavailable [104].
Literature revealed that tannins can form complexes with metal ions as well as target macromolecular polysaccharides and proteins [105]. Hence, these compounds may interact with enzymes through their interaction with any zinc moiety thus preventing its activity. In addition, some studies have significantly proven their selective binding of PGN, PLN and EA to NS3 protease enzymes at their substrate binding sites and this is further supported by molecular docking studies [23,104]. It is noted that molecules 156 and 157 possess galloyl residues that provide further evidence for their inhibitory effects against NS3/4A protease. decreasing antiapoptotic factors including HuR (human antigen R), HO-1 (Heme oxygenase-1) and SIRT1 (silent information regulator). It also decreases apoptotic markers including IL-6 (interleukin-6) and TGF-β (transforming growth factor -β) in cell line of prostatic cancer [106]. Compound 158 also mediates the apoptotic process in cancer cells of the pancreas through inhibiting NF-kB and the mitochondrial depolarization process [107] and demonstrated an anticancer effect through decreasing the expression of genes involved in oxidative stress [108].

Phloroglucinol
Myrciarone A (159) and rhodomyrtone (160) (Figure 19) are produced by the fruit peels of Myrciaria dubia and were screened for their antimicrobial effects where it was found that these compounds displayed potent antimicrobial effects towards Bacillus subtilis and B. cereus with MIC: 1.56 and 0.78 µ g/mL, respectively. Notably, the activities of metabolite 159 against B. subtilis and Streptococcus aureus were equal to the standard kanamycin, whereas the effects of the same compound against B. cereus and Micrococcus luteus were 4-fold higher than the standard kanamycin (MIC: 6.25 µ g/mL) [109].
The activities of rhodomyrtone (160) towards B. cereus and M. luteus (MIC: 0.78 µ g/mL) were 8-fold higher than kanamycin (MIC: 6.25 µ g/mL). The antimicrobial effects of molecule 160 against S. mutans (MIC: 1.56 µ g/mL) were equal to the standard kanamycin, whereas the same compound was 2-fold more active towards S. aureus (MIC: 0.78 µ g/mL) and S. epidermidis. Myrciarone A (159) displayed the same level of activities against S. epidermidis and S. mutans with MIC: 3.13 µ g/mL and its effects were 2-fold less than kanamycin (MIC: 1.56 µ g/mL). Metabolites 159 and 160 were unfortunately not active towards Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Candida albicans and Saccharomyces cerevisiae [109]. Further study revealed that compounds 156-158 demonstrated biological effects towards RNA replication of HCV and the exact mechanism of this activity is yet to be investigated. Since compounds 156-158 inhibit NS3 protease, thus affecting HCV polyprotein proteolytic processing which in turn leads to a decreased active viral RNA-dependent RNA polymerase level. This eventually causes a decreasing level of HCV RNA [104]. Of note is that tannin 158 results in apoptosis in the cell line of human prostatic cancer by decreasing antiapoptotic factors including HuR (human antigen R), HO-1 (Heme oxygenase-1) and SIRT1 (silent information regulator). It also decreases apoptotic markers including IL-6 (interleukin-6) and TGF-β (transforming growth factor -β) in cell line of prostatic cancer [106]. Compound 158 also mediates the apoptotic process in cancer cells of the pancreas through inhibiting NF-kB and the mitochondrial depolarization process [107] and demonstrated an anticancer effect through decreasing the expression of genes involved in oxidative stress [108].

Phloroglucinol
Myrciarone A (159) and rhodomyrtone (160) (Figure 19) are produced by the fruit peels of Myrciaria dubia and were screened for their antimicrobial effects where it was found that these compounds displayed potent antimicrobial effects towards Bacillus subtilis and B. cereus with MIC: 1.56 and 0.78 µg/mL, respectively. Notably, the activities of metabolite 159 against B. subtilis and Streptococcus aureus were equal to the standard kanamycin, whereas the effects of the same compound against B. cereus and Micrococcus luteus were 4-fold higher than the standard kanamycin (MIC: 6.25 µg/mL) [109].
RNA polymerase level. This eventually causes a decreasing level of HCV RNA [104]. Of note is that tannin 158 results in apoptosis in the cell line of human prostatic cancer by decreasing antiapoptotic factors including HuR (human antigen R), HO-1 (Heme oxygenase-1) and SIRT1 (silent information regulator). It also decreases apoptotic markers including IL-6 (interleukin-6) and TGF-β (transforming growth factor -β) in cell line of prostatic cancer [106]. Compound 158 also mediates the apoptotic process in cancer cells of the pancreas through inhibiting NF-kB and the mitochondrial depolarization process [107] and demonstrated an anticancer effect through decreasing the expression of genes involved in oxidative stress [108].

Phloroglucinol
Myrciarone A (159) and rhodomyrtone (160) (Figure 19) are produced by the fruit peels of Myrciaria dubia and were screened for their antimicrobial effects where it was found that these compounds displayed potent antimicrobial effects towards Bacillus subtilis and B. cereus with MIC: 1.56 and 0.78 µ g/mL, respectively. Notably, the activities of metabolite 159 against B. subtilis and Streptococcus aureus were equal to the standard kanamycin, whereas the effects of the same compound against B. cereus and Micrococcus luteus were 4-fold higher than the standard kanamycin (MIC: 6.25 µ g/mL) [109].

Peptides
Pepstatin A (203) (Figure 24) was reported from Punica granatum fruit peel [56]. This peptide is a potent inhibitor of aspartic proteases (AP) with an inhibition constant (Ki) of 0.1 nM. Notably, semisynthetic derivatives of pepstatin have led to the discovery of potent AP inhibitors. Research showed that the statyl part of this peptide is thought to be responsible for the pepsin inhibition [119]. Two cyclic peptides 204 and 205 produced by the fruit peels of C. medica had their structures established via extensive spectroscopic techniques [120].

Peptides
Pepstatin A (203) (Figure 24) was reported from Punica granatum fruit peel [56]. This peptide is a potent inhibitor of aspartic proteases (AP) with an inhibition constant (Ki) of 0.1 nM. Notably, semisynthetic derivatives of pepstatin have led to the discovery of potent AP inhibitors. Research showed that the statyl part of this peptide is thought to be responsible for the pepsin inhibition [119]. Two cyclic peptides 204 and 205 produced by the fruit peels of C. medica had their structures established via extensive spectroscopic techniques [120].

Peptides
Pepstatin A (203) (Figure 24) was reported from Punica granatum fruit peel [56]. This peptide is a potent inhibitor of aspartic proteases (AP) with an inhibition constant (Ki) of 0.1 nM. Notably, semisynthetic derivatives of pepstatin have led to the discovery of potent AP inhibitors. Research showed that the statyl part of this peptide is thought to be responsible for the pepsin inhibition [119]. Two cyclic peptides 204 and 205 produced by the fruit peels of C. medica had their structures established via extensive spectroscopic techniques [120].

Miscellaneous
The tetranortriterpenoid, kokosanolide D (206) (Figure 25) was reported from Lansium domesticum fruit peels [121]. Biphenyl ether 207 was isolated from the fruit peel of Elaeagnus rhamnoides. In antiviral screening, compound 207 was found to cause a 3.49 log 10 reduction in HSV-2 yield and this metabolite also possesses antiviral effects in the qPCR method [39]. Citrusoside A (208) was isolated from the peels of Citrus hystrix fruits and possesses butyrylcholinesterase inhibition activity with IC 50 : 376 µM [31].

Fruit Peels and Food Industries
A good number of countries have directed their industry to enhance their food supply sequence effectively because that will decrease food loss and waste. In order to counteract this issue, including active agents viz., antioxidant and antimicrobial molecules or extracts, into packaging materials is considered a feasible solution in order to increase food shelf life, decrease food losses and enhance the wealth of the food industry. Natural products, biopolymers and extracts are reported to maintain the safety and biocompatibility of the material addressing consumer health concerns.
A great number of natural products have been isolated from fruit peels and these compounds illustrated antimicrobial, antioxidant and cytotoxic effects. In addition, Table  1 illustrates that many fruit peel extracts and essential oils possess antimicrobial and antioxidant effects [29,30,. Utilization of fruit peels can become a possible food industry, cosmetic industry and as a source for producing beneficial drugs. With a marked antibacterial potential, fruit-peel-derived natural products, extracts and essential oils could be utilized as antibacterial agents in food processing and storage. For instance, these peel-derived materials could suppress the spoilage bacteria, mainly Pseudomonas antarctica. These peel-derived materials revealed significant antibacterial effects towards pathogenic Staphylococcus aureus which causes food poisoning.
Antioxidants from natural sources are valuable bioactive compounds with welldemonstrated potentials for use in the food industry. Lipid oxidation along with microbial

Fruit Peels and Food Industries
A good number of countries have directed their industry to enhance their food supply sequence effectively because that will decrease food loss and waste. In order to counteract this issue, including active agents viz., antioxidant and antimicrobial molecules or extracts, into packaging materials is considered a feasible solution in order to increase food shelf life, decrease food losses and enhance the wealth of the food industry. Natural products, biopolymers and extracts are reported to maintain the safety and biocompatibility of the material addressing consumer health concerns.
A great number of natural products have been isolated from fruit peels and these compounds illustrated antimicrobial, antioxidant and cytotoxic effects. In addition, Table 1 illustrates that many fruit peel extracts and essential oils possess antimicrobial and antioxidant effects [29,30,. Utilization of fruit peels can become a possible food industry, cosmetic industry and as a source for producing beneficial drugs. With a marked antibacterial potential, fruit-peel-derived natural products, extracts and essential oils could be utilized as antibacterial agents in food processing and storage. For instance, these peel-derived materials could suppress the spoilage bacteria, mainly Pseudomonas antarctica. These peel-derived materials revealed significant antibacterial effects towards pathogenic Staphylococcus aureus which causes food poisoning.
Antioxidants from natural sources are valuable bioactive compounds with welldemonstrated potentials for use in the food industry. Lipid oxidation along with microbial growth are the major cause of spoilage of foods, such as nuts, meats, fish, sauces, milk powders and oils. Fruit-peel-derived natural products, extracts and essential oils demonstrated significant antioxidant capacity and could be employed as a substitute for synthetic antioxidants to enhance the shelf life of foods.
Pomegranate peel is reported to be a source of cellulose [164]. Cellulose is a biodegradable polymer and can be utilized in different food applications since it has been used in biomedical applications, such as carriers in drug delivery. Pectins are carbohydrate macromolecules present in citrus fruit peels, apple pomace and mango peels. Pectins are employed as an ingredient or additive for food in the preparation of jellies, jams and marmalades [164]. Coconut (Cocos nucifera) Antioxidant: E showed significant effects [147] E: Extract(s); EO: Essential oils.

Fruit-Peel-Based Edible Coatings/Film and Probiotics
Edible coatings are applied as thin layers on the food surface and results in longer food shelf life, retention of food characteristics, properties and functionality at low cost. Shin et al. [165] developed an apple-peel-based edible coating which was used to keep beef patties fresh. This coating was screened for antioxidant effects towards lipid oxidation along with antimicrobial effects towards yeasts, molds and mesophilic aerobic bacteria. Results demonstrated that this coating treatment inhibited lipid oxidation and effectively suppressed the growth of tested microbial entities on raw beef patties. In another study, Al-Anbar et al. [166] established an orange-peel-based edible coating and this protocol was found to enhance the shelf life of cupcakes. It was found that this coating has the ability to enhance storage age, reduce microbial growth and prevent growth of any yeast or mold during storage time. Moghadam et al. [167] established edible films which were derived from mung bean protein supplemented with pomegranate peel. Of note, this film demonstrated significant antioxidant and antibacterial effects and can be used for the packaging of food products. The combined effects of orange peel (Citrus sinensis) essential oil (OPEO) with chitosan film increased the shelf life of fresh shrimps (Parapenaeus longirostris) to 15 days [168].
In another study, the lemon peel essential oil possessed potent antimicrobial effects against Escherichia coli and Bacillus sp. and the addition of this essential oil with an edible coating (sodium alginate and cassava starch) significantly decreases the degradation of fresh strawberry and tofu [169]. In addition, nanoemulsion-based edible coatings comprising OPEO can increase the shelf life [170] of orange slices while a combination of gelatin coating and (OPEO) extended shrimp quality by about 6 days [171]. Probiotic yogurt which was prepared with pineapple peel powder enhances antibacterial activity against Escherichia coli, as well as anticancer and antioxidant effects [172]. It was discovered that the addition of banana, apple and passion fruit peel powder in probiotic yogurt enhances the growth of Lactobacillus casei, L. acidophilus and L. paracasei [173]. In addition, mango peels exhibit a positive effect in milk supplementation [174] and orange, passion fruit and pineapple peel enhance the firmness and consumer acceptability in yogurt [175].

Conclusions and Future Perspective
Fruit peels, which form a significant portion as a food processing by-product, have not yet been employed as a useful resource for many health supportive products. It is abundantly clear from this review that the potential possibilities to utilize these bioactive components in the food chain are available to the pharmaceutical industry. One of the possible factors for such an unused resource is an erroneous general misconception that fruit peels are unhealthy and considered an undesired waste. The current review has undoubtedly established that fruit peels are indeed a very rich resource of biologically active natural compounds and will have significant benefits for human and animal health. Investing in the fruit peel processing industry, food processors may expand their usability and flexibility to include a fruit-peel-based novel products business venture to establish a profitable existing enterprise. Producing healthy foods with natural ingredients or with fruit peels could bring so many new advantages via the reduction or elimination of food preservatives, artificial additives and replacing them with cheap natural ingredients. In addition, fruit and vegetable peels are being widely employed as food additives and in the modern era of health-conscious young people, such a venture will add to their repertoire of food buying possibilities.

Conflicts of Interest:
The authors declare no conflict of interest.