Crude terpene glycoside component from Radix paeoniae rubra protects against isoproterenol-induced myocardial ischemic injury via activation of the PI3K/AKT/mTOR signaling pathway

被引：48

作者：

Ke, Zhongcheng ^{[1
,2
,3
]}

Wang, Gang ^{[3
]}

Yang, Lei ^{[3
]}

Qiu, Huihui ^{[3
]}

Wu, Hao ^{[3
]}

Du, Mei ^{[3
]}

Chen, Juan ^{[3
]}

Song, Jie ^{[3
]}

Jia, Xiaobin ^{[1
,3
]}

Feng, Liang ^{[1
,3
]}

机构：

[1] Nanjing Univ Chinese Med, Nanjing 210023, Jiangsu, Peoples R China

[2] Huangshan Univ, Coll Chem & Chem Engn, Huangshan 245041, Anhui, Peoples R China

[3] Jiangsu Prov Acad Chinese Med, Key Lab New Drug Delivery Syst Chinese Mat Med, Nanjing 210028, Jiangsu, Peoples R China

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2017年 / 206卷

基金：

中国国家自然科学基金;

关键词：

REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; RATS; APOPTOSIS; CARDIOPROTECTION; PAEONIFLORIN; STRESS; ACID; PROLIFERATION; INHIBITION;

D O I：

10.1016/j.jep.2017.05.028

中图分类号：

Q94 [植物学];

学科分类号：

071001 [植物学];

摘要：

Ethnopharmacological relevance: Radix paeoniae rubra, also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis. It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown. This study was conducted to explore the protective and curative effects of CS-TG against isoproterenol (ISO)-induced myocardial ischemic injury in rats and investigate the underlying myocardial protective mechanisms. Materials and methods: A rat model of ISO-induced myocardial ischemia was established to evaluate the protective effect of CS-TG in ameliorating heart injury. Myocardial ischemia was induced by administering ISO (40 mg/kg/d) subcutaneously for 2 days. Serum was collected and analyzed for the levels of different cardiac biomarkers, and heart tissues were isolated and prepared for ATP analysis, glycogen content determination, histopathology assay, and ultrastructure observation. The regulatory effects of CS-TG on myocardial apoptosis in rats were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of cleaved caspase-3, Bax, and Bcl-2 were detected by western blotting. Furthermore, in vitro experiments were conducted to examine whether the CS-TG's cardioprotective effects were linked to the inhibition of apoptosis via activation of the phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Results: CS-TG (300 mg/kg/d) significantly decreased serum levels of creatine kinase and lactate dehydrogenase in ISO-induced myocardial ischemic rats. Analysis of ATP and glycogen contents, myocardial ultrastructure, and pathological examination showed that CS-TG (300 mg/kg/d) significantly improved energy metabolism and alleviated myocardial injury in vivo. In addition, the expression of p-AKT and p-mTOR in rats subjected to CS TG significantly elevated, while the levels of caspase-3 and Bax/Bcl-2 dramatically reduced. Moreover, treatment with LY294002, a PI3K inhibitor, abrogated CS-TG (200 mu g/mL) induced down-regulation of cleaved caspase-3, Bax/Bcl-2 in the serum. Conclusions: CS-TG protects the heart from ISO-induced myocardial ischemia, potentially by improving cardiac energy metabolism and inhibiting cardiomyocyte apoptosis via activation of the PI3K/AKT/mTOR signaling pathway. Thus, CS-TG might be a potential therapeutic candidate for the prevention and treatment of myocardial ischemia.

引用

页码：160 / 169

页数：10

共 39 条

[1]

Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production [J].