Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats.

BACKGROUND: Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats' livers. METHODS: STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR. RESULTS: Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P < 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P < 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P < 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P < 0.05) and decrease MDA levels (P < 0.001) compared to diabetic control group. CONCLUSIONS: Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

The anti-diabetic effects of betanin in streptozotocin-induced diabetic rats through modulating AMPK/SIRT1/NF-κB signaling pathway.

BACKGROUND: In the last few years, the effects of bioactive food components have received much attention because of their beneficial effects including decreasing inflammation, scavenging free radicals, and regulating cell signaling pathways. Betanin as a potent antioxidant has been previously reported to exhibit anti diabetic effects. The present study aimed to evaluate the effects of betanin on glycemic control, lipid profile, hepatic function tests, as well as the gene expression levels of 5' adenosine monophosphate­activated protein kinase (AMPK), sirtuin-1 (SIRT1), and nuclear factor kappa B (NF­κB) in streptozocin (STZ) induced diabetic rats. METHODS: Diabetes was induced in male Sprague-Dawley rats by intraperitoneal administration of STZ. Different doses of betanin (10, 20 and 40 mg/kg.b.w) was administered to diabetic rats for 28 days. Fasting blood glucose and serum insulin were measured. The histopathology of liver and pancreas tissue evaluated. Real-time PCR was performed to assess gene expression levels. RESULTS: Treatment of diabetic rats with betanin (10 and 20 mg/kg.b.w) reduced FBG levels compared to the control diabetic rats (P < 0.001). Betanin at the dose of 20 mg/kg.b.w was most effective in increasing serum insulin levels (P < 0.001) improving glucose tolerance test (GTT) as well as improvement in lipid profile and liver enzymes levels. According to histopathologic assay, different damages induced by STZ to liver and pancreas tissues was largely eliminated by treatment with 10 and 20 mg/kg.b.w of betanin. Betanin also significantly upregulated the AMPK and SIRT1 and downregulated the NF-κB mRNA expression compared to the diabetic control rats (P < 0.05). CONCLUSION: Betanin could modulate AMPK/SIRT1/NF-κB signaling pathway and this may be one of its anti-diabetic molecular mechanisms.