足细胞
糖尿病肾病
化学
内分泌学
内科学
药理学
肾
胰岛素抵抗
链脲佐菌素
激酶
医学
胰岛素
糖尿病
生物化学
蛋白尿
作者
Chuanping Zhao,Zejiang Pu,Jian Gao,Chang Liu,Jianzhong Xing,Wenbo Lang,Jinting Chen,Chun‐Mao Yuan,Chengyan Zhou
标识
DOI:10.1021/acs.jafc.2c05595
摘要
We explored the protection of mangiferin monosodium salt (MGM) on kidney injury in rats with streptozotocin (STZ)-induced diabetic nephropathy (DN) by "multiomics" analysis combined with systems pharmacology, with a specific focus on ferroptosis, inflammation, and podocyte insulin resistance (IR) signaling events in kidneys. MGM treatment afforded renoprotective effects on rats with STZ-induced DN by alleviating systemic IR-induced renal inflammation and podocyte IR. These mechanisms were correlated mainly with the MGM treatment-induced inhibition of the mitogen-activated protein kinase/nuclear factor-kappa B axis and activation of the phosphorylated insulin receptor substrate 1(Tyr608)/phosphorylated phosphatidylinositol 3-kinase/phosphorylated protein kinase B axis in the kidneys of DN rats. MGM had an ameliorative function in renal ferroptosis in rats with STZ-induced DN by upregulating mevalonate-mediated antioxidant capacities (glutathione peroxidase 4 and ferroptosis suppressor protein 1/coenzyme Q10 axis) and weakening acyl-CoA synthetase long-chain family member 4-mediated proferroptotic generation of lipid drivers in kidneys. MGM may be a promising alternative strategy for the treatment of DN.
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