Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling.
BACKGROUND
Salvianolic acid B (Sal B) is one of the most bioactive components of Salvia miltiorrhiza, a traditional Chinese herbal medicine that has been commonly used for prevention and treatment of cerebrovascular disorders. However, the mechanism responsible for such protective effects remains largely unknown. It has been considered that cerebral endothelium apoptosis caused by reactive oxygen species including hydrogen peroxide (H(2)O(2)) is implicated in the pathogenesis of cerebrovascular disorders.


RESULTS
By examining the effect of Sal B on H(2)O(2)-induced apoptosis in rat cerebral microvascular endothelial cells (rCMECs), we found that Sal B pretreatment significantly attenuated H(2)O(2)-induced apoptosis in rCMECs. We next examined the signaling cascade(s) involved in Sal B-mediated anti-apoptotic effects. We showed that H(2)O(2) induces rCMECs apoptosis mainly through the PI3K/ERK pathway, since a PI3K inhibitor (LY294002) blocked ERK activation caused by H(2)O(2 )and a specific inhibitor of MEK (U0126) protected cells from apoptosis. On the other hand, blockage of the PI3K/Akt pathway abrogated the protective effect conferred by Sal B and potentated H(2)O(2)-induced apoptosis, suggesting that Sal B prevents H(2)O(2)-induced apoptosis predominantly through the PI3K/Akt (upstream of ERK) pathway.


CONCLUSIONS
Our findings provide the first evidence that H(2)O(2) induces rCMECs apoptosis via the PI3K/MEK/ERK pathway and that Sal B protects rCMECs against H(2)O(2)-induced apoptosis through the PI3K/Akt/Raf/MEK/ERK pathway.
Liu
Chen-Li
CL
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
Xie
Li-Xia
LX
Li
Min
M
Durairajan
Siva Sundara Kumar
SS
Goto
Shinya
S
Huang
Jian-Dong
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053630:Depsides
D001572:Benzofurans; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C076944:salvianolic acid B; D053630:Depsides