Maackiain Protects the Kidneys of Type 2 Diabetic Rats via Modulating the Nrf2/HO-1 and TLR4/NF-κB/Caspase-3 Pathways.

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is aglobal health burden that accounts for about 90% of all cases of diabetes. Injury to the kidneys is aserious complication of type 2 diabetes. Maackiain, apterocarpan extracted from roots of Sophora flavescens, has been traditionally used for various disease conditions. However, nothing is known about its possible potential effect on HFD/STZ-T2D-induced nephrotoxicity. METHODS: In this study, T2D rat model is created by high-fat diet (HFD) for 2 weeks with injection of asingle dose of streptozotocin (35mg/kg body weight). T2D rats were orally administered with maackiain (10 and 20mg/kg body weight) for 7 weeks. RESULTS: Maackiain suppressed T2D-induced alterations in metabolic parameters, lipid profile and kidney functionality markers. By administering 10 and 20mg/kg maackiain to T2D rats, it was able to reduce lipid peroxidation while improving antioxidant levels (SOD, CAT, and GSH). Furthermore, the present study demonstrated the molecular mechanisms through which maackiain attenuated T2D-induced oxidative stress (mRNA Nrf2, Nqo-1, Ho-1, Gclc and Gpx-1; protein NRF2, NQO-1, HO-1 and NOX-4), inflammation (mRNA Tlr, Myd88, IκBα, Mcp-1, Tgf-ß, col4, Icam1, Vcam1 and E-selectin; Protein TLR4, MYD88, NF-κB, IκBα, MCP-1; levels TNF-α and MCP-1) and apoptosis (mRNA Bcl-2, Bax, Bad, Apaf-1, Caspase-9 and Caspase-3; protein Bcl-2, Bax, Caspase-3 and Caspase-9) mediated renal injury. Additionally, significant improvement in kidney architecture was observed after treatment of diabetic rats with 10 or 20mg/kg maackiain. CONCLUSION: Maackiain protects the kidney by decreasing oxidative stress, inflammation, and apoptosis to preserve normal renal function in type 2 diabetes.