Acta Pharmacologica Sinica (2009) 30: 159-165; doi: 10.1038/aps.2008.25; published online 19th January 2009

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-3β, 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-3β 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.

Keywords: geniposide; glucagon-like peptide 1 receptor; PI3K; GSK-3β; PDK1