Apigenin attenuates high-fat diet-induced nephropathy in rats by hypoglycemic and hypolipidemic effects, and concomitant activation of the Nrf2/antioxidant axis

Abstract

• The protective potential of apigenin in rats with high-fat diet (HFD)-induced nephropathy by activation of Nrf2. • Apigenin reduced body weight. • Apigenin improved hyperglycemia, hyperinsulinemia, hyperlipidemia and renal tubular damage. • Apigenin increased the mRNA, cytoplasmic, and nuclear levels of Nrf2. • Apigenin reduced levels of GSH, SOD, CAT, MDA, TNF-α, IL-6. This study examined the protective potential of apigenin in rats with high-fat diet (HFD)-induced nephropathy, and tested its involvement in the activation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Control, apigenin, HFD, HFD + apigenin, and HFD + Nrf2 inhibitor (brusatol) groups were formed. Apigenin was administered orally (50 mg/kg), and all treatments were conducted for 12 weeks. Apigenin, administered orally (50 mg/kg), significantly reduced body weight and reversed hyperglycemia, hyperinsulinemia, hyperlipidemia, renal tubular damage, and interstitial collagen deposition induced by HFD-fed rats. Additionally, apigenin significantly increased the mRNA, cytoplasmic, and nuclear levels of Nrf2 and levels of glutathione, superoxide dismutase, and catalase, but significantly reduced the levels of malondialdehyde, tumor necrosis factor-alpha, and interleukin-6, nuclear levels of nuclear factor kappa beta p65, and mRNA levels of transforming growth factor-β1, Bax, and caspase-3. Brusatol co-treatment abolished all the effects of apigenin on these markers, except for body and fat weights, glucose, and insulin. In conclusion, apigenin attenuated HFD-induced nephropathy by activating Nrf2.