Stachydrine (Sta), a major constituent of Leonurus japonicus Houtt, has been reported to possess numerous cardioprotective effects. In this study, we evaluated the effect of Sta on pressure overload-induced diastolic heart failure in rats and investigated the mechanisms underlying the effect. Wistar rats were randomized to transverse aortic constriction (TAC) or sham operation. After 3 days, the rats that underwent TAC were randomized to treatment for a total of four experimental groups (n=10 each group): sham operation, TAC only, TAC + telmisartan (Tel), and TAC + stachydrine (Sta). After 12 weeks, we evaluated left ventricular hypertrophy, function, and fibrosis by echocardiography, pressure-volume loop analysis, and histology. In addition, levels of fibrosis-related proteins in the heart were determined by Western blot analysis. Our results showed that Sta significantly suppressed TAC-induced cardiac hypertrophy, and TAC-induced increases in heart weight/body weight and heart weight/tibial length. In addition, Sta attenuated TAC-induced decreases in left ventricular ejection fraction and improved other hemodynamic parameters. Compared with the TAC only group, rats treated with Sta exhibited significant decreases in interstitial and perivascular fibrosis, TGF-beta R1 protein levels, and phosphorylation of Smad2/3; however, protein levels of TGF-beta 1, TGF-beta R2, and Smad4 did not differ significantly between the two groups. Taken together, our results demonstrate that Sta protects against diastolic heart failure by attenuating myocardial hypertrophy and fibrosis via the TGF-beta/Smad pathway.
[1]Shanghai Univ Tradit Chinese Med, Dept Pathol, 1200 Cailun Road, Shanghai 201203, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Publ Expt Platform, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Ctr Drug Safety Evaluat Res, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Dept Physiol, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
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