Kaempferol Inhibits Inflammation via Regulating the Pi3k/Akt/Nuclear Factor Kappa B Pathway and Promotes Autophagy by Regulating the Pi3k/Akt/Mammalian Target of Rapamycin Pathway to Improve Podocyte Injury Induced By Antibody in Lupus Nephritis

Abstract Objective: This study aimed to explore the protective effects of kaempferol against podocyte injury in lupus nephritis (LN) and its underlying mechanism. Materials and Methods: Human podocytes were co-cultured with immunoglobulin G (IgG) from patients with LN (IgG-LN) to simulate podocyte injury in LN. Levels of oxidative stress and inflammatory factors were measured using the different kits. The expression of podocyte injury marker proteins was detected using immunofluorescence and western blotting. Then, we explored the interactions of kaempferol with PI3K, Akt, and nuclear factor kappa B (NF-κB) by molecular docking. Furthermore, PI3K agonists (740 Y-P) and inhibitors (LY294002) were used to explore the mechanism by which kaempferol alleviates IgG-LN-induced podocyte injury. Autophagy was measured by western blotting and Monodansylcadaverine staining. Results: The results indicated that kaempferol could protect podocyte injury induced by IgG-LN in a dose-dependent manner. Kaempferol significantly reduced oxidative stress, increased the activity of antioxidant enzymes, and reduced the levels of inflammatory factors in IgG-LN-treated podocytes. Kaempferol could bind to the active sites of PI3K, Akt, and NF-κB with high affinity, especially to NF-κB. LY294002 enhanced the ameliorative effect of kaempferol against IgG-LN-induced podocyte injury, whereas 740 Y-P weakened this protective effect. Compared to the model group, kaempferol significantly reduced the p-mTOR/mammalian target of rapamycin (mTOR) ratio and activated autophagy. Conclusions: Kaempferol can inhibit inflammation and oxidative stress through the regulation of PI3K/Akt/NF-κB pathway and promote autophagy by regulating the PI3K/Akt/mTOR pathway to improve IgG-LN induced podocyte injury.