Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity
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Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.
This work was supported by grants from the National Natural Science Foundation of China (81130014, 81471046 and 81530024), the European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CDC)/Lilly Program for Collaborative Diabetes Research between China and Europe, and Innovative Funding for Translational Research from Tongji Hospital.
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