Rutin from Lonicera japonica inhibits myocardial ischemia/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1/2 and PI3K/Akt signals in vitro

被引:120
作者
Jeong, Jae Ju [1 ,2 ]
Ha, Yu Mi [1 ,2 ]
Jin, Yong Chun [3 ]
Lee, Eun Ju [4 ,5 ]
Kim, Ju Sun [4 ,5 ]
Kim, Hye Jung [1 ,2 ]
Seo, Han Geuk [1 ,2 ]
Lee, Jae Heun [1 ,2 ]
Kang, Sam Sik [4 ,5 ]
Kim, Yeung Shik [4 ,5 ]
Chang, Ki Churl [1 ,2 ]
机构
[1] Gyeongsang Natl Univ, Sch Med, Dept Pharmacol, Jinju, South Korea
[2] Gyeongsang Natl Univ, Inst Hlth Sci, Jinju, South Korea
[3] Yanbian Univ, Affiliated Hosp, Dept Cardiovasc Surg, Yanji 133000, Peoples R China
[4] Seoul Natl Univ, Coll Pharm, Seoul, South Korea
[5] Seoul Natl Univ, Inst Nat Prod Res, Seoul, South Korea
关键词
Apoptosis; Ischemia reperfusion injury; Rutin; aPI3kinase; ERK1/2; pathway; Oxidative stress; ISCHEMIA-REPERFUSION; ENDOTHELIAL-CELLS; EXPRESSION; KINASE; DEATH; ANTIOXIDANT; MODULATION; QUERCETIN; PATHWAYS; HEARTS;
D O I
10.1016/j.fct.2009.03.044
中图分类号
TS2 [食品工业];
学科分类号
100403 [营养与食品卫生学];
摘要
We investigated pharmacological effects of rutin isolated form Lonicera japonica on H2O2-induced cell death in H9c2 cells in vitro and rat myocardial ischemia-reperfusion injury model in vivo. Western blot analysis showed that H2O2 increased expression of cleaved form of caspase-3 and proapoptotic Bax protein, but decreased antiapoptotic Bcl-2 protein in H9c2 cell. However, treatment with rutin decreased expression of both cleaved from of caspase-3 and increased Bcl-2/Bax ratio in H9c2 cells. The protective effect of rutin was inhibited not by JNK inhibitor or p38 MAPK inhibitor but by PI3K inhibitor or ERK inhibitor. Rutin increased phosphorylation of ERK and Akt in H9c2 cells. These anti-apoptotic effects of rutin were confirmed both by annexin-V and TUNEL assay. Furthermore, rutin improved I/R-induced myocardial contractile function and reduced infarct size. Rutin administration also inhibited apoptosis in myocardial tissues in I/R rats by increasing Bcl-2/bax ratio and decreasing active caspase-3 expression. These results suggest that rutin reduced oxidative stress-mediated myocardial damage in vitro model and in vivo model, which might be useful in treatment of myocardial infarction. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1569 / 1576
页数:8
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