The aqueous extract of Gentianella acuta improves isoproterenol‑induced myocardial fibrosis via inhibition of the TGF‑β1/Smads signaling pathway

Abstract

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 hematoxylineosin, 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.

Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization

“…Myofibroblasts can express a contractile protein such as α-SMA and produce excessive collagen during fibrosis progression (Weber and Diez, 2016;Song et al, 2020). Our previous studies demonstrated that TGF-β1 expression was upregulated in fibrotic heart tissue, and G. acuta downregulated the upregulation and ameliorated myocardial fibrosis by inhibiting TGF-β1 signaling Yang et al, 2020). This work evaluated the effect of BEL, a vital component of G. acuta, on cell viability with or without TGF-β1.…”

“…In these regions, Ewenki people keep a habit of drinking "guixincao" tea, and employ it to treat angina by water decoction or chewing for a long time (Wunir et al, 2009;Li et al, 2010). Our previous studies demonstrated that TGF-β1 was elevated in isoprenaline (ISO)induced cardiac fibrotic tissue, and G. acuta ameliorated myocardial fibrosis by inhibiting TGF-β1/Smads signaling Yang et al, 2020).…”

Bellidifolin Inhibits SRY-Related High Mobility Group-Box Gene 9 to Block TGF-β Signalling Activation to Ameliorate Myocardial Fibrosis

“…In Inner Mongolia, G. acuta has been applied to treat angina by the local herdsmen, and increasing studies have reported that it can protect the heart from injury [ 20 ]. We have verified that G. acuta and its xanthone compound BEL could alleviate myocardial fibrosis by preventing TGF- β 1 signalling [ 19 , 21 ]. The present study further illuminated the mechanism of BEL on myocardial fibrosis in vivo and in vitro.…”

The remodel of the “central dogma”: a metabolomics interaction perspective

“…In macrophages, Lys311 is a key succinylated site in the regulation of PKM2 activity, promoting inflammation (Wang et al, 2017 ). O-GlcNAcylation plays an important role in the regulation of cellular signaling, translation, and transcription in response to nutrients and stresses (Li et al, 2019 ; Ong et al, 2018 ); glycosylation is important in the correct folding and trafficking of proteins, such as Relmα, CD206, and CD301, which are destined for secretion or exportation to the cell surface in anti-inflammatory macrophages (Jha et al, 2015 ).…”