Tanshinone IIA attenuates neuronal damage and the impairment of long-term potentiation induced by hydrogen peroxide.
OBJECTIVE
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 (H(2)O(2))-induced oxidative stress in rats.


METHODS
H(2)O(2)-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 H(2)O(2).


RESULTS
It was found that pretreatment with Tan IIA protected primary rat cortical neurons against H(2)O(2)-induced cytotoxicity. Furthermore, Tan IIA markedly reduced the elevation of [Ca(2+)](i) evoked by H(2)O(2). Western blot analysis indicated that pretreatment with Tan IIA prevented the increase in Bax/Bcl-2 ratio induced by H(2)O(2). In addition, preincubation of Tan IIA 20 min prior to H(2)O(2) exposure could reverse H(2)O(2)-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.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wei
W
Wang
Li-Li
LL
Zheng
Fang
F
Wang
Zhuang-Li
ZL
Hu
Wen-Ning
WN
Wu
Jun
J
Gu
Jian-Guo
JG
Chen
D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; C021751:tanshinone; D006861:Hydrogen Peroxide