3-O-demethylswertipunicoside inhibits MPP+-induced oxidative stress and apoptosis in PC12 cells

The 3-O-demethylswertipunicoside (3-ODS) is extracted from Swertia punicea. Recent study from our laboratory has demonstrated that the 3-ODS protects against oxidative toxicity and apoptosis in PC12 cells (Zhang, S.P., Du, X.G., Pu, X.P., 2010. Biol. Pharm. Bull. 33, 1529–1533). The aim of our study is to further investigate the neuroprotective mechanisms of 3-ODS in 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in PC12 cells. The results indicated that pre-treatment with 3-ODS significantly increased the cell viability compared with MPP+ treatment. It also alleviated the oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) level and reactive oxygen specise (ROS) production. Moreover, 3-ODS also attenuated MPP+-induced apoptosis by inhibiting Bax and Bcl-2 expressions, activating caspase-9, caspase-3, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, apoptosis-inducing factor (AIF) translocation and α-synuclein expression. These results suggest that 3-ODS might has applications as a complementary medicine for the treatment of Parkinson's disease (PD) or other neurodegenerative diseases.

► 3-ODS prevented MPP+-induced neurotoxicity in PC12 cells. ► 3-ODS alleviated oxidative stress by regulating SOD, MDA and ROS levels. ► The expression of anti-apoptotic protein Bax was down-regulated by 3-ODS. ► Caspases-mediated signaling pathway was involved in the mechanism of 3-ODS. ► 3-ODS also inhibited AIF translocation and α-synuclein aggregation.