title: Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways.
abstract: Quercetin (Que), a plant-derived flavonoid, possesses various biological functions. Moreover, Que exerts multiple beneficial actions in treatment of cardiovascular diseases and there are an inverse association between Que intakes and occurrence and development of various cardiovascular diseases. Some researchers have inferred that the mechanisms of Que to protect cardiomyocytes from ischemia/reperfusion (I/R) injury may be involved in modulation of intracellular signal pathways and regulation of proteins expression in vivo. The current study investigated whether Que has any protective effects on cardiomyocytes from hypoxia/reoxygenation (H/R) in vitro and its potential cardioprotective mechanisms. The cell viability of Que on H9c2 cardiomyoblast cells was assessed by MTT. Apoptosis was evaluated by both Hoechst33342 staining and Flow cytometric analysis (FACS). Furthermore, the effect of Que, SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor) on mitogen-activated protein kinases (MAPKs) and the expression of apoptosis related proteins (Bcl-2, Bax and caspase-3) was determined by Western blotting. MTT assays showed that pretreatment with Que could increase the viability of H9c2 cardiomyocytes that suffered H/R. Both Hoechst33342 staining and FACS confirmed that Que could remarkably suppress the H/R-induced apoptotic cardiomyocytes. In addition, Que significantly alleviated H/R-induced the phosphorylation of JNK and p38, which further increased Bcl-2 expression and inhibited the activation of Bax and caspase-3 directly or indirectly. In summary, our results imply that Que can induce cardioprotection by inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways and modulate the expression of Bcl-2 and Bax proteins that provides a new experimental foundation for myocardial ischemia disease therapy.
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China. Electronic address: biolichengqiu@126.com.
authors.forename: Chengqiu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China.
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China.
authors.forename: Jichang
authors.initials: J
authors.lastname: Xuan
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Medicine, The Zoucheng People's Hospital, Jining, Shandong 273500, PR China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011794:Quercetin; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Cardiomyocytes; Hypoxia/reoxygenation; JNK; Quercetin; p38