The potential therapeutic effects of Trifolium alexandrinum extract, hesperetin and quercetin against diabetic nephropathy via attenuation of oxidative stress, inflammation, GSK-3β and apoptosis in male rats.

Diabetic nephropathy (DN) is one of the manifestations of systemic microangiopathy in diabetes. Trifolium alexandrinum extract (TAE) contains biologically active phenolic compounds such as hesperetin (HES) and quercetin, possess various pharmacological properties, including anti-inflammatory, and anti-oxidative potentials. The present study aimed to assess the therapeutic effects and mechanisms underlying the anti-diabetic, antioxidant, and anti-inflammatory effects of HES and quercetin extracted from TAE, and TAE in STZ-induced DN. Male albino rats (170 ± 10 g) were divided into group (1); control rats and groups (2-5); diabetic/HFD were intraperitoneal (i.p.) injected with STZ (35 mg/kg), diabetic rats were randomly classified into STZ, STZ + HES (40 mg/kg), STZ + quercetin (50 mg/kg), and STZ + TAE (200 mg/kg) groups. After 5 weeks, blood and kidney samples were collected for further biochemical, western blotting and histopathological studies. Serum renal functions, renal oxidative status biomarkers and proinflammatory cytokines were determined. The results revealed that there were significant increases in urea, BUN, creatinine, ALP, total protein, albumin, and globulin with a significant decrease in Na and K levels, as well as significant elevation in TBARS, TGF-β, TNF-α, IL-6 and the expression levels of GSK-3β, as well as significant decline in TAC, GSH and CAT levels in STZ-treated group compared to the control rats. The previous deleterious alterations were significantly ameliorated after the treatment of diabetic rats with HES, quercetin and TAE. In conclusion, our data demonstrated that HES, quercetin and TAE could be used as potent therapeutic agents to counter DN through antioxidant, anti-inflammatory, and antidiabetic effects.