Abstract
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 H2O2-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H2O2-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 H2O2-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 H2O2-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 H2O2-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H2O2-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.
Highlights
Increasing evidences have revealed that oxidative stress is closely related to neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease
Primary antibodies for PI3K, phosphorylation- (p-) PI3K, AKT, and p-AKT were obtained from the ImmunoWay Biotechnology Co. (Suzhou, China)
cell counting kit-8 (CCK-8) assay results showed that 90 μM H2O2 treatment could significantly decrease the viability of PC12 cells, making them 40% lower than the normal group (P < 0:01) (Figures 1(a) and 1(d))
Summary
Increasing evidences have revealed that oxidative stress is closely related to neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Excessive reactive oxygen species (ROS) is commonly considered the main cause corresponding to oxidative stress [1,2,3]. ROS, such as hydrogen peroxide (H2O2), superoxide anions, and hydroxyl radicals, can stimulate cells which cause structural damage including lipid peroxidation and DNA and protein oxidation, promote oxidative stress, and disrupt the redox balance of the body, as well as change the normal function and morphology of cells [4]. Excessive ROS is closely related to mitochondrial dysfunction and can increase intracellular Ca2+ concentration and activate some intracellular apoptotic pathways. The PI3K/Akt signaling pathway is closely correlated to it, which is involved in the changes of Bcl-2 family proteins and the activation of caspase family proteins [7]
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