Antidiabetic Potency, Antioxidant Effects, and Mode of Actions ofCitrus reticulataFruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats

Abstract

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

Naringin and Hesperidin Counteract Diclofenac‐Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti‐Inflammatory, and Antiapoptotic Activities

“…Thus, based on the results of the present study and of past publications, it can be suggested that the ameliorative effects of naringin and hesperidin, singly or in combination, on liver function and structural integrity may be attributed to their suppressive effects on the inflammation, oxidative stress, and apoptosis and to their stimulatory effects on antiinflammatory effects on antioxidant defense system (Figure 6). This suggestion was supported by previous publications which stated the antioxidant and anti-inflammatory effects of naringin and hesperidin in different diseased conditions and drug toxicities [65][66][67][68][69][70][71][72][73][74][75].…”

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity

“…Similar results were found in ob/ob diabetic mice supplemented with the flavonoid nobiletin (200 mg/kg bw) [48]. Moreover, the oral administration of citrus fruit peel extracts and its constituting flavonoids naringin, naringenin, hesperidin and quercetin at a dose of 100 mg/kg bw for 4 weeks significantly recovered the suppressed mRNA expressions of GLUT-4 and IRβ-subunit in the adipose tissue of nicotinamide (NA)/streptozotocin-STZ/NA-induced type 2 diabetic rats [49,50]. Accordingly, the improved insulin sensitivity in the adipose tissue had potent anti-hyperglycemic and anti-hyperlipidemic effects in STZ/NA-induced diabetic rats.…”

Musa paradisiacaL. leaf and fruit peel hydroethanolic extracts improved the lipid profile, glycemic index and oxidative stress in nicotinamide/streptozotocin‐induced diabetic rats

“…Nicotinamide (NA)/streptozotocin (STZ)‐induced DM is most commonly used as animal model of T2DM in rats to validate the effect and to scrutinize the mechanisms of action of new therapeutic agents. In this model, there are both moderate impairment in insulin secretion and insulin resistance, which is a characteristic feature of T2DM (Ali et al., 2020; Gorinstein et al., 2007; Singh & Singh, 2010; Zhou et al., 2009).…”