Citrus Peel Polyphenols: Recent Updates and Perspectives
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Int. J. Biosci. 2020 International Journal of Biosciences | IJB | ISSN: 2220-6655 (Print), 2222-5234 (Online) http://www.innspub.net Vol. 16, No. 2, p. 53-70, 2020 RESEARCH PAPER OPEN ACCESS CITRUS PEEL POLYPHENOLS: RECENT UPDATES AND PERSPECTIVES Muhammad Imran, Shahnai Basharat, Sidra Khalid, Maria Aslam, Fatima Syed, Shaista Jabeen, Hafsa Kamran, Muhammad Zia Shahid*, Tabussam Tufail, Faiz-ul- Hassan Shah, Awais Raza University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, University of Lahore, Lahore-Pakistan Key words: Citrus peel, Polyphenols, Anti-oxidants, Health benefits, Toxicity. http://dx.doi.org/10.12692/ijb/16.2.53-70 Article published on February 05, 2020 Abstract Enormous amount of agro-wastes is producing annually during the processing of fruits and vegetables. These by- products are prominent and promising source of bioactive compounds which exhibits health endorsing perspectives such as prevention from cancer insurgence, diabetes preventive, and protection from cardiovascular complications, anti-aging, and prevention from oxidative stress due to their strong antioxidant potential. Among these agro-wastes,citrus peels are rich source of polyphenols as flavanones, flavones, flavonols and anthocyanins and have health protective effect and act as a potential nutraceutical in the treatment of various non- communicable diseases. These bioactive moieties act as antioxidant thereby scavenging free radical activity and reducing oxidative stress which is cause of burden of diseases. Polyphenols has been used as prebiotic in mitigating gut microbiome and a solution for gastrointestinal disorders. Citrus polyphenols exert health promoting effect in regulating lipid metabolism and treating neurodegenerative diseases. * Corresponding Author: Muhammad Zia Shahid [email protected] 53 Imran et al. Int. J. Biosci. 2020 Introduction extracts (CPFE) and flavonoid compounds; Polyphenols are secondary plant metabolites that act tangeretin, hesperidin, and nobiletin, citrus flavonoid as prebiotic and have disease protective benefits in purity mixture (CFPM), have lipid-lowering effects on certain form of cancers, cardiovascular diseases, oleic acid-induced lipid accumulation in HepG2 cells. diabetes associated oxidative stress and most CPFE and CFPM suppressed miR-122 and miR-33 importantly protecting the DNA against oxidative expression, increase in the damage(Kawabata et al., 2019).Among these, citrus carnitinepalmitoyltransferase 1α (CPT1α) gene and, fruits peels contain phenolic and flavonoids decrease in fatty acid synthase (FAS) gene in oleic compounds which have health protective effect. These acid-treated HepG2 cells by regulating lipid flavonoids have various types as metabolism, (Su et al., 2019). Bioactive compounds flavanones, flavones, flavonols. Citrus peel contains can be produced by recycling of agro-industrial waste. anthocyanins in the form of hydroxycinnamic Phytochemical constituents found in Citrus peels of andhydroxybenzoic acids (Belisteri et al., 2019). lemon, grapefruit, and mandarin exerts antigenotxic, Naringenin is a flavanone as polyphenol and has antiproliferation, anticancer and antioxidant many therapeutic benefits in reducing and activities. Ethanol 98% was used for extraction of eliminating inflammation, oxidative stress and other three peels of lemon, grapefruit, and mandarin to neurological disorders(Joshi et al., 2018).A study assess total flavonoid content (TFC), total polyphenol conducted by Casacchiaand their co-workers, they content (TPC), and antioxidant activity using DPPH explored that citrus peel polyphenols have inhibitory (1, 1-diphenyl-2-picrylhydrazyl). Results revealed that action on human enzyme amylase and lipaseto treat TPC was found highest in lemon peel, TFC in and manage human disorders due to their antioxidant mandarin peels and antioxidant activity was greater potential(Casacchia et al., 2019). in lemon peel exerting radical scavenging activity by DPPH at 50% effective concentration(EC50= 42.97 µg Polyphenols are obtained from different varieties of extract/ mL) and Trolox equivalent antioxidant citrus fruits. They include gallic acid, quercetin, capacity (TEAC=0.157). Moderate cytotoxic activity sinapic acid, chlorogenic acid,ferulic acid, myricetin, (IC50 = 77.8 µg/mL) was observed in Mandarin peel and kaempferol including the new compounds of against human leukemia HL-60 cells, (Diab, 2016). tetra-O-methylscutella and heptamethoxy flavone are new compounds derived fromkaempferol, chlorogenic A study conducted by He, Li, Peng, He, & Pan, to acid sinapic acid, myricetin,ferulic acid, quercetin, determine the anti-melanogenic and anti-oxidant and gallic acid as well as nutritional flavonoids like effects of peel derived from pomelo cv. Guan Xi naringin, hesperidin, total flavones, glycosyl (Ahmed named as pomelo peel essential oil (PPEO). Analysis et al., 2019).Citrus by-products are promising and of PPEO exposed volatile chemical components as β- prominent source of bioactive compounds such as pinene (3.16%), limonene (55.92%), and β-myrcene (431–4131 mg/100 g DW) andhesperidin (131– (31.17%). Effects of PPEO on the B16 melanoma cell 5433 mg/100 g DW), (Thieme et al., 2019).In dose system showed concentrations below50 μg/mL dependent manner, citrus polyphenols significantly decrease the melanin content and inhibiting suppressed the formation of micronuclei and lowered tyrosinase (TYR) activity. PPEO antioxidant activity is the micronucleated polychromatic erythrocytes in showed against superoxide anion free radicals, 2,2′- bone marrow cells of rats (Chandrappa et al., 2017). azinobis-(3-ethylbenzthiazoline-6-sulphonate(ABTS), and 2,2-diphenyl-2-picryhydrazyl (DPPH) (He, Li, Flavonoids found in citrus plants are beneficial for Peng, He, & Pan, 2019). lipid metabolism. Su et a l(2019) carried out a study to find the lipid lowering effect of poly phenols in Citrus polyphenols have cardioprotective effect but human hepatoma cell line. Citrus peel flavonoids because of poor bioavailability its hypolipidemic 54 Imran et al. Int. J. Biosci. 2020 effects are not properly achieved. Mollace et al., decreased the cholesterol level. Almost, all samples conducted a Double Blind, randomized, Placebo- reduced triacylglyceride (36%–80.6%) than reference Controlled Study to evaluate Hypolipemic and drug (35%), also, glucose was reduced (71.1%–82.8 Hypoglycemic effects of standard bergamot and 68.6%–79.6%) mainly by the aqueous polyphenolic fraction (BPF®) as well as of its homogenates and alcoholic extracts of Citrus fruits phytosomal formulation (BPF Phyto) in diabetic and peels better than the reference drug used (by 68.3%). hyperlipemic patients. Results revealed hypolipemic All the extracted pectin, from the four types, has effect by increasing HDL level, reducing LDL marked effect on the three parameters. For the first atherogenic particles and overall reduction in fasting time these findings confirmed the comparative HPLC plasma glucose exerting hypoglycemic effect, quantification of nobiletin and biological studies of (Mollace, et al., 2019). different citrus peels varieties as agro-waste products, (Fayeket al., 2017). Health endorsing perspectives Diabetes prevention Wahyuono and co fellows, 2017, analyzed the citrus Ernawita and colleagues, 2016, using HPLC analysis peel and pulp samples from Indonesia and reported examined that Violaxanthin (Z)- and violaxanthin antioxidant property, inhibition of α-amylase and (all-E)- were the basic carotenoids of the peel, while antibacterial activities of sample. Most of the extract the major carotenoids of the pulp of jeruktakengon contained lower doses of α-carotene, β-carotene and were (all-E) β-cryptoxanthin and (Z)-violaxanthin. β-cryptoxanthin, zeaxanthin, and lutein. The extract The peel extract showed increased antioxidant also enclosedhesperidin, naringin,polymethoxylated, activity as compared to the pulp extract, and this sinensetinneohesperidin, quercetin and tangeretin. L- activity was further enhanced by the process TEAC (lipophilic trolox equivalent antioxidant saponification. Peel extracts due to their qualities of capacity) test used for the extract of peel showed antioxidant, antibacterial and α-amylase inhibitory higher antioxidant activity in comparison to extract of activity, showed biological potential, (Ernawita et al., pulp. All the extracts showed α-amylase inhibitory 2016).Sathiyabama and fellow researchers, 2018, activity; extract of pulp showed increased inhibitory studied fruit peel of Citrus sinensis (CSMe), rats were activity then the extract of peel, (Wahyuono et al., given CSMe (50 and 100 mg/kg) and results showed 2017). decreased levels of plasma insulin (22.9% and 32.7%, respectively) and blood glucose of fasting (56.1% and Alu'datt and colleagues, 2107, investigatedselective 55.7%, respectively) in comparison to rats with plants of the citrus family by their phenolic untreated diabetic control. Peel of citrus invert the compounds which showed antioxidant and phenolic biochemical abnormalities and also showed an extract-mediated inhibitory activities using increase in the strength of the positive spectrophotometry for α-glucosidase and α-amylase. immunoreactions for insulin in pancreatic islets and A large amount of free phenolic content was explored their cytoprotective activity in diabetic rats. Peel of for sample (85.43-92.82% of TPC) in comparison to citrus dose augmented the activity of PPARγ in the the bounded form (7.18-14.57% of TPC). adipose tissue