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.
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.
Jeong
Jae Ju
JJ
Department of Pharmacology, School of Medicine, and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Ha
Yu Mi
YM
Jin
Yong Chun
YC
Lee
Eun Ju
EJ
Kim
Ju Sun
JS
Kim
Hye Jung
HJ
Seo
Han Geuk
HG
Lee
Jae Heun
JH
Kang
Sam Sik
SS
Kim
Yeung Shik
YS
Chang
Ki Churl
KC
D000818:Animals; D017304:Annexin A5 / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D031239:Lonicera / Q000737:chemistry*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D016877:Oxidants / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D012431:Rutin / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
D017304:Annexin A5; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D012431:Rutin; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C022616:thiazolyl blue