Puerarin inhibits NHE1 activity by interfering with the p38 pathway and attenuates mitochondrial damage induced by myocardial calcium overload in heart failure rats  

作　　者：Guopin Pan Baoyue Cui Mingming Han Laibiao Lin Yinlan Li Ling Wang Shuang Guo Yaling Yin Heqin Zhan Peng Li 

机构地区：[1]Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology,Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention,School of Basic Medical Sciences,College of Pharmacy,Xinxiang Medical University,Xinxiang 453003,China [2]Hubei Key Laboratory of Diabetes and Angiopathy,Hubei University of Science and Technology,Xianning 437100,China [3]Nanyang Second General Hospital,Nanyang 473001,China [4]College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第2期270-279,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.82271460 and U1804197);the Research Foundation of Henan Province(Nos.202300410308 and HNGD2022067);the National High-End Foreign Expert Recruitment Plan of China(No.G2022026006L);the Research Foundation of Xinxiang Medical University(Nos.XYBSKYZZ505319 and XYBSKYZZ201626).

摘　　要：Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases.The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases(protective effect on cardiomyocytes)is still unclear.In the present study,we identify the role of puerarin in an animal model of experimental heart failure(HF)and explore its underlying mechanisms.The HF rat model is induced by in-traperitoneal injection of adriamycin(ADR),and puerarin is administered intragastrically at low,medium,and high concentrations.We demonstrate that puerarin significantly improves myocardial fibrosis and inflammatory in-filtration and,as a result,improves cardiac function in ADR-induced HF rats.Mechanistically,we find for the first time that puerarin inhibits overactivated Na+/H+exchange isoform 1(NHE1)in HF,which may improve HF by decreasing Na+and Ca2+ion concentrations and attenuating mitochondrial damage caused by calcium overload;on the other hand,puerarin inhibits the activation of the p38 pathway in HF,reduces the expressions of TGF-βand proinflammatory cytokines,and suppresses myocardial fibrosis.In conclusion,our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of p38 and its downstream NHE1.

关 键 词：PUERARIN p38 pathway NHE1 heart failure TGF-β proinflammatory cytokines 

分 类 号：R54[医药卫生—心血管疾病] R28[医药卫生—内科学]