Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway

Aim: Oxidative stress plays a critical role in the pathogenic cascade leading to neuronal degeneration in AD. Consequently, the induction of endogenous antioxidative proteins by antioxidants seems to be a very reasonable strategy for delaying the disease's progression. In previous work, we identified the neurotrophic and neuroprotective effects of geniposide, which result from the activation of glucagon-like peptide 1 receptor (GLP-1R). In this study, we explore the role of PI3 kinase signaling pathway in the neuroprotection of geniposide in PC12 cells. Methods: Cell viability was determined by MTT assay. Apoptosis was detected by Hoechst and PI double staining. The protein expression of Bcl-2 and phosphorylation of Akt308, Akt473, GSK-3 beta, and PDK1 was measured by Western blot. Results: Geniposide induced the expression of the antiapoptotic protein Bcl-2, which inhibited apoptosis in PC12 cells induced by H2O2, and this effect could be inhibited by preincubation with LY294002, a selective inhibitor of PI3K. Furthermore, geniposide enhanced the phosphorylation of Akt308, Akt473, GSK-3 beta and PDK1 under conditions of oxidative stress. Conclusion: These results demonstrate that the PI3K signaling pathway is involved in the neuroprotection of geniposide in PC12 cells against the oxidative damage induced by H2O2 in PC12 cells.