A preliminary study on the protective mechanism of ursolic acid against pres-sure over-load induced cardiac hypertrophy

Shi Guangyong; Zhang Bing; Zhao Lin; Chen Yawu; Jin Zhenxiao; Xu Xuezeng

doi:10.13498/j.cnki.chin.j.ecc.2023.05.11

Abstract：Objective To investigate the effect and mechanism of ursolic acid on myocardial hypertrophy.Methods Pri-mary cardiomyocytes from lactating mice were isolated and cultured,and cardiomyocyte hypertrophy was induced by phenyleph-rine(PE).The mean cross-sectional area of cardiomyocytes was calculated by immunofluorescence staining,intracellular reactive oxygen species(ROS)were detected by dichlorofluorescein diacetate(DCFH-DA)staining,and the transcription and expression levels of hypertrophic and antioxidation-related molecules in cardiomyocytes were evaluated by quantitative polymerase chain re-action(PCR)and western blotting.Results Ursolic acid significantly decreased the cross-sectional area of myocytes induced by PE(P<0.05),and decreased the transcription levels of hypertrophic molecules Nppb and Myh7(P<0.01),and the expression lev-els of hypertrophic molecules BNP(P<0.001)and β-MHC(P<0.01).Ursolic acid significantly inhibited ROS levels in PE in-duced cardiomyocytes(P<0.01),and increased the expression levels of SOD2 and CAT(P<0.01)and PGC-1α(P<0.001).After the administration of SR-18292,an inhibitor of PGC-1α,the ability of ursolic acid to reduce myocyte hypertrophy,inhibit tran-scription and expression of hypertrophy related molecules,decrease intracellular ROS levels,and increase intracellular antioxi-dant enzymes after PE treatment was disappeared.Conclusion Ursolic acid exerts resistance to cardiac hypertrophy by enhanc-ing the expression of PGC-1α,increasing the expression of the intracellular antioxidant enzymes SOD2 and CAT,and decreasing intracellular ROS levels in cardiomyocytes.