Tanshinone IIA attenuates neuronal damage and the impairment of long-term potentiation induced by hydrogen peroxide

Aim of the study: Tanshinone IIA (Tan IIA) is one of the key components of Salvia miltiorrhiza Bunge that has been widely used for various cardiovascular and cerebrovascular disorders in Asian countries. Many studies have reported that Tan IIA has antioxidative properties, but whether Tan IIA can rescue neurons from oxidative insult has never been reported. The present study was undertaken to evaluate the possible neuroprotective effects of Tan IIA on hydrogen peroxide (H2O2)-induced oxidative stress in rats. Materials and methods: H2O2-induced cytotoxicity was evaluated by the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and flow cytometry with PI staining. Calcium imaging experiments were carried out to measure intracellular free calcium concentration. Western blotting was used to determine the expression of Bax and Bcl-2 protein. Electrophysiological studies in hippocampal slices were performed to investigate the effect of Tan IIA on synaptic function and cognitive impairment caused by H2O2. Results: It was found that pretreatment with Tan HA protected primary rat cortical neurons against H2O2-induced cytotoxicity. Furthermore, Tan IIA markedly reduced the elevation of [Ca2+](i) evoked by H2O2. Western blot analysis indicated that pretreatment with Tan HA prevented the increase in Bax/Bcl-2 ratio induced by H2O2. In addition, preincubation of Tan IIA 20 min prior to H2O2 exposure could reverse H2O2-induced hippocampal LTP impairment, but without significant alteration in basal synaptic transmission and LTP induction. Conclusions: These findings demonstrate that Tan IIA might serve as a novel promising therapeutic agent for oxidative stress injury in neurodegenerative diseases. (C) 2010 Elsevier Ireland Ltd. All rights reserved.