Stachydrine ameliorates pressure overload-induced diastolic heart failure by suppressing myocardial fibrosis

Stachydrine (Sta), a major constituent of Leonurus japonicus Houtt, has been reported to possess numer- ous 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 trans- verse 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 ad- dition, 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 intersti- tial and perivascular fibrosis, TGF-βR1 protein levels, and phosphorylation of Smad2/3; however, protein levels of TGF-β1, TGF-βR2, and Smad4 did not differ significantly between the two groups. Taken together, our results dem- onstrate that Sta protects against diastolic heart failure by attenuating myocardial hypertrophy and fibrosis via the TGF-β/Smad pathway.