Therapeutic Potential of Bioactive Flavonoids from Citrus Fruit Peels toward Obesity and Diabetes Mellitus

Abstract

Obesity is associated with a significantly increased risk of cardiovascular and metabolic diseases such as diabetes mellitus. Recently, a growing body of evidence shows that phytochemicals, especially many flavonoids, place an inhibitory regulatory effect on adipogenesis, obesity and diabetes. With computer-aided drug discovery, the action modes of more and more bioactive flavonoids are being identified and confirmed at the molecular level. Citrus fruit peels are particularly rich in bioactive flavonoids which have demonstrated strong therapeutic potentials in regulating lipid metabolisms. However, they are usually thrown away after consuming the flesh, sometimes even causing environmental problems. Thus, extraction of useful flavonoids from citrus fruit waste for pharmaceutical industry could be a profitable and environmentally friendly solution in the future, advocating the concepts of circular economy and sustainable society. The aim of this review is to summarize current evidence on the antiobesity and antidiabetic potentials of identified bioactive flavonoids extracted from the peels of citrus fruits. Our results suggest that various citrus fruit peels could be potential sources for novel drugs and nutraceuticals. Combining experimental data and artificial intelligence methods to study citrus flavonoids would facilitate the discovery of novel drugs against obesity and obesity-related metabolic diseases.

Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

“…The flavonoids in C. pinnatifida leaves have shown hypolipidemic activity through multiple mechanisms, including inhibiting cholesterol absorption, adipogenesis, and hepatic lipogenesis and increasing hepatic fatty acid oxidation [ 37 ]. Citrus flavonoids, especially naringin, naringenin, nobiletin, and hesperidin, are well known to reverse obesity and related metabolic abnormalities through the regulation of lipid metabolism, improvement in insulin resistance, and suppression of inflammatory responses in adipose tissue [ 38 , 39 , 40 ].…”

Functional foods of sub‐Saharan Africa and their implications in the management of type 2 diabetes: A review

“…Many phytochemicals in fruits that have antioxidant properties can protect β‐cells from oxidative damage. It is the case with citrus fruits that contain active compounds like flavanones (neohesperidin, narirutin, naringin, naringenin, hesperidin, eriocitrin, and didymin), flavones (5‐hydroxy‐3,6,7,8,3′,4′‐hexamethoxyflavone, 5‐demethylnobiletin, 3′,4′,3,5,6,7,8 heptamethoxyflavone, tangeretin, sudachitin, sinensetin, nobiletin, diosmin, and diosmetin) and others flavonoids (anthocyanins, cigranoside C, D, E, F, and quercetin) (Lu & Yip, 2023 ). Didymin substantially inhibited advanced glycation end products, rat lens aldose reductase, human recombinant aldose reductase, protein tyrosine phosphatase 1B, and α‐glucosidase.…”

Naringenin and Hesperidin as Promising Alternatives for Prevention and Co-Adjuvant Therapy for Breast Cancer

“…The phenolic compounds found in citrus fruits have been shown to have several positive impacts on the body, including reducing inflammation [ 24 ], improving cardiovascular health [ 25 ], and protecting against oxidative stress-related disorders [ 26 , 27 ]. Several in vitro and in vivo studies have shown that flavonoids, especially flavanones, the main class of flavonoids in citrus extracts, such as naringin and naringenin [ 22 , 28 ], possess antiproliferative, anti-inflammatory, and pro-apoptotic properties [ 29 , 30 , 31 , 32 , 33 , 34 ]. Other compounds found in citrus fruits that have demonstrated potential anticancer effects include quercetin [ 15 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], hesperidin [ 42 , 43 , 44 ], hesperetin [ 45 , 46 ], polymethoxyflavones [ 47 , 48 , 49 ], eriodyctiol [ 50 , 51 ], bergapten [ 52 , 53 ], tangeretin [ 54 , 55 ], auraptene [ 56 , 57 , 58 ], limonin [ 59 ], naringenin [ 60 , 61 , 62 , 63 , 64 , 65 ], and naringin [ …”