The aqueous extract of Gentianella acuta improves isoproterenol-induced myocardial fibrosis via inhibition of the TGF-[beta]1/Smads signaling pathway

Gentianella acuta (G. acuta) is one of the most commonly used herbs in Chinese Mongolian medicine for the treatment of heart disease. Previously, it was found that G. acuta ameliorated cardiac function and inhibited isoproterenol (ISO)-induced myocardial fibrosis in rats. In this study, the underlying anti-fibrotic mechanism of G. acuta was further elucidated. Histopathological changes in the heart were observed by hematoxylin-eosin, Masson trichrome and wheat germ agglutinin staining. Relevant molecular events were investigated using immunohistochemistry and western blotting. The results revealed that G. acuta caused improvements in myocardial injury and fibrosis. G. acuta also inhibited collagens I and III and [alpha]-smooth muscle actin production in heart tissue. G. acuta downregulated the expression of transforming growth factor [beta]1 (TGF-[beta]1) and notably inhibited the levels of phosphorylation of TGF-[beta] receptors I and II. Furthermore, G. acuta caused downregulation of the intracellular mothers against decapentaplegic homolog (Smads)2 and 4 expression and inhibited Smads2 and 3 phosphorylation. The results further demonstrated that the mechanism underlying anti-myocardial fibrosis effects of G. acuta was based upon the suppression of the TGF-[beta]1/Smads signaling pathway. Therefore, G. acuta may be a potential therapeutic agent for ameliorating myocardial fibrosis. Key words: Gentianella acuta, isoproterenol, myocardial fibrosis, transforming growth factor-[beta]1, transforming growth factor-[beta]1/mothers against decapentaplegic homolog signaling pathway