Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

Molecular Medicine, November 2015

26552059

Shuang Hu, Yuxing Zhang, Meng Zhang, Yanchao Guo, Ping Yang, Shu Zhang, Sakine Simsekyilmaz, Jun-Fa Xu, Jinxiu Li, Xudong Xiang, Qilin Yu, Cong-Yi Wang

Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with potential to treat inflammatory and allergic diseases as well as tumor. Herein in the present report, we demonstrated that pre-treatment with aloperine provided protection for mice against ischemia reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis along with well preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NFκB 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, and through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes. the expression of anti-apoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults such as in the setting of renal transplantation could be a viable approach to prevent IR-induced injuries.