6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway  

作　　者：Shu-qing Ma Zhen Guo Fang-yuan Liu Shahzad-Gul Hasan Dan Yang Nan Tang Peng An Ming-yu Wang Hai-ming Wu Zheng Yang Di Fan Qi-zhu Tang 

机构地区：[1]Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan 430060,China [2]Cardiovascular Research Institute of Wuhan University,Wuhan 430060,China [3]Hubei Key Laboratory of Metabolic and Chronic Diseases,Wuhan 430060,China [4]Department of Medicine,Bahawal Victoria Hospital,Bahawalpur 63100,Pakistan

出　　处：《Acta Pharmacologica Sinica》2021年第10期1575-1586,共12页中国药理学报（英文版）

基　　金：The present study was supported by grants from the National Natural Science Foundation of China(81900219,81530012,and 81800216);the Fundamental Research Funds for the Central Universities(2042019kf0062 and 2042018kf1032);the Development Center for Medical Science and Technology National Health and Family Planning Commission of China(2016ZX-008-01);the National Key R&D Program of China(2018YFC1311300).

摘　　要：6-Gingerol,a pungent ingredient of ginger,has been reported to possess anti-inflammatory and antioxidant activities,but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive.In this study,we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models,and to clarify the underlying mechanisms.C57BL/6 mice were subjected to transverse aortic constriction(TAC),and treated with 6-gingerol(20 mg/kg,ig)three times a week(1 week in advance and continued until the end of the experiment).Four weeks after TAC surgery,the mice were subjected to echocardiography,and then sacrificed to harvest the hearts for analysis.For in vitro study,neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine(PE)and transforming growth factor-β(TGF-β)challenge.We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy,fibrosis,inflammation,and dysfunction in TAC mice.In the in vitro study,we showed that treatment with 6-gingerol(20μM)blocked PE-induced-cardiomyocyte hypertrophy and TGF-β-induced cardiac fibroblast activation.Furthermore,6-gingerol treatment significantly decreased mitogen-activated protein kinase p38(p38)phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro,which was upregulated in the absence of 6-gingerol treatment.Moreover,transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses(Ad-MKK6),which specifically activated p38,abolished the protective effects of 6-gingerol in both in vitro and in vivo models.In conclusion,6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner.The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.

关 键 词：6-GINGEROL pressure overload cardiac remodeling mitogen-activated protein kinase p38 CARDIOMYOCYTES cardiac fibroblasts PHENYLEPHRINE TGF-β 

分 类 号：R96[医药卫生—药理学] R54[医药卫生—药学]