2,3,5,4＇-Tetra hyd roxystil bene-2-O-β-D-gl ucoside protects murine hearts against ischemia/reperfusion injury by activating Notchl/Hesl signaling and attenuating endoplasmic reticulum stress

2,3,5,4＇-Tetrahydroxystilbene-2-O-β-D-glucoside （TSG） is a water-soluble active component extracted from Polygonum multiflorum Thunb. A number of studies demonstrate that TSG exerts cardioprotective effects. Since endoplasmic reticulum （ER） stress plays a key role in myocardial ischemia/reperfusion...

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Published in:中国药理学报：英文版 2017, Vol.38 (3), p.317-330
Main Author: Meng ZHANG Li-ming YU Hang ZHAO Xuan-xuan ZHOU Qian YANG Fan SONG Li YAN Meng-en ZHAI Bu-ying LI Bin ZHANG Zhen-xiao JIN Wei-xun DUAN Si-wang WANG
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Language:English
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Summary:2,3,5,4＇-Tetrahydroxystilbene-2-O-β-D-glucoside （TSG） is a water-soluble active component extracted from Polygonum multiflorum Thunb. A number of studies demonstrate that TSG exerts cardioprotective effects. Since endoplasmic reticulum （ER） stress plays a key role in myocardial ischemia/reperfusion （MI/R）-induced cell apoptosis, we sought to determine whether modulation of the ER stress during MI/R injury was involved in the cardioprotective action of TSG. Male mice were treated with TSG （60 mg.kg^-1.d^-1, ig） for 2 weeks and then were subjected to MI/R surgery. Pre-administration of TSG significantly improved post-operative cardiac function, and suppressed MI/R-induced myocardial apoptosJs, evidenced by the reduction in the myocardial apoptotic index, serum levels of LDH and CK after 6 h of reperfusion. TSG （0.1-1000 pmoi/L） did not affect the viability of cultured H9c2 cardiomyoblasts in vitro, but pretreatment with TSG dose-dependently decreased simulated ischemia/reperfusion （SlR）-induced cell apoptosis. Furthermore, both in vivo and in vitro studies revealed that TSG treatment activated the Notchl/Hesl signaling pathway and suppressed ER stress, as evidenced by increasing Notch1, Notch1 intracellular domain （NICD）, Hesl, and Bcl-2 expression levels and by decreasing p-PERK/ PERK ratio, p-elF2~/elF2（x ratio, and ATF4, CHOP, Bax, and caspase-3 expression levels. Moreover, the protective effects conferred by TSG on SIR-treated H9c2 cardiomyoblasts were abolished by co-administration of DAPT （the Notch1 signaling inhibitor）. In summary, TSG ameliorates MI/R injury in vivo and in vitro by activating the Notchl/Hesl signaling pathway and attenuating ER stress-induced apoptosis.
ISSN:1671-4083
1745-7254