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

Jiahong Guo,1 Junying Li,2 Hua Wei,1 Zhaozhi Liang1 1Department of Nephrology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, 453000, People’s Republic of China; 2Department of Nephrology, The Affiliated Hospital of Qingdao University Pingdu district, Pingdu City, Qingdao, Shandong, 266000, People’s Republic of ChinaCorrespondence: Junying LiDepartment of Nephrology, The Affiliated Hospital of Qingdao University Pingdu District, No.369 Shanghai Road, Qingdao, Pingdu City, Shandong, 266000, People’s Republic of ChinaEmail lijunying2020@sina.cnBackground: 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-β, 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.Keywords: high-fat diet, streptozotocin, oxidative stress, inflammation, apoptosis, kidney