Hydroxy-α-sanshool Possesses Protective Potentials on H(2)O(2)-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-α-sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H(2)O(2)-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H(2)O(2)-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H(2)O(2)-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H(2)O(2)-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H(2)O(2)-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H(2)O(2)-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.