Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
Department of Medical Laboratory Science, College of Integration of Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
Int J Mol Med. 2020 Jan;45(1):223-233. doi: 10.3892/ijmm.2019.4410. Epub 2019 Nov 21.
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 α‑smooth muscle actin production in heart tissue. G. acuta downregulated the expression of transforming growth factor β1 (TGF‑β1) and notably inhibited the levels of phosphorylation of TGF‑β 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‑β1/Smads signaling pathway. Therefore, G. acuta may be a potential therapeutic agent for ameliorating myocardial fibrosis.
獐牙菜（G. acuta）是蒙医药中治疗心脏病最常用的草药之一。先前发现獐牙菜可改善大鼠心功能并抑制异丙肾上腺素（ISO）诱导的心肌纤维化。在本研究中，进一步阐明了獐牙菜的潜在抗纤维化机制。通过苏木精-伊红、Masson 三色和麦胚凝集素染色观察心脏的组织病理学变化。使用免疫组织化学和蛋白质印迹法研究相关分子事件。结果表明，獐牙菜可改善心肌损伤和纤维化。獐牙菜还抑制心脏组织中胶原 I 和 III 以及α-平滑肌肌动蛋白的产生。獐牙菜下调转化生长因子β1（TGF-β1）的表达，并显著抑制 TGF-β受体 I 和 II 的磷酸化水平。此外，獐牙菜导致细胞内母亲抗 decapentaplegic 同源物（Smads）2 和 4 的表达下调，并抑制 Smads2 和 3 的磷酸化。结果进一步表明，獐牙菜抗心肌纤维化作用的机制基于抑制 TGF-β1/Smads 信号通路。因此，獐牙菜可能是改善心肌纤维化的潜在治疗剂。
