Astragaloside Inhibits Hepatic Fibrosis by Modulation of TGF-β1/Smad Signaling Pathway

Abstract

Activation of HSC is a pivotal step in hepatic fibrosis. In the activation of HSC, the TGF-β1 plays a key role that can promote the occurrence of hepatic fibrosis by combining with Smad proteins. Astragaloside is the main active component extracted from Radix Astragali that has the effect of antioxidation and hepatoprotection. In the present study, we investigated the mechanism of astragalosides inhibiting hepatic fibrosis in vitro and in vivo. In vitro, astragalosides inhibited the activation of HSC and regulated the expression of MMP-2 and TIMP-2 and reduced the formation of collagen fibers. In vivo, administration of astragalosides decreased the serum ALT, AST, and TBiL in rats by reducing oxidative stress. Astragalosides also attenuated hepatic fibrosis by reducing the concentration of hydroxyproline and inhibiting the formation of collagen fibers. The expressions of TGF-β1, TβR-I, p-Smad 2, and p-Smad 3 were downregulated after astragalosides treatments, while Smad 7 was upregulated compared to the control group. The results indicated that the effect of astragaloside on hepatic fibrosis was related to the inhibition of HSC activation and the modulation of the TGF-β1/Smad signaling pathway.

Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF‑β1/Smad/miR‑192 signaling pathway

“…Astragaloside IV (ASI) is the major active constituent of Astragalus membranaceus (also known as huangqi) and has been widely used for the treatment of cardiovascular diseases, hepatitis, kidney disease and skin diseases in China (13,14). The hepatoprotective and antifibrotic effects of ASI have been supported in previous studies (15,16). Despite the increase in the clinical usage of ASI, the mechanisms underlying its therapeutic effects on DN remain not clearly understood and require further investigation.…”

“…Based on the results of previous studies, it can be hypothesized that the therapeutic and antifibrotic effects of ASI on DN are associated with the TGF-β1/Smad signaling pathway (13–16). Therefore, the current study established a rat mesangial cell (RMC) model, induced by high glucose (HG), and a DN rat model to assess this.…”

Irbesartan ameliorates myocardial fibrosis in diabetic cardiomyopathy rats by inhibiting the TGFβ1/Smad2/3 pathway

“…In a positive feedback mechanism, the protein complex acts on the promoter region of the TGFβ1 gene to promote its expression and TGFβ1 autocrine signalling. In addition, TGFβ1 plays a positive feedback role by promoting the expression of the TβR-I and TβR-II receptor genes and amplifying the TGFβ1/Smad2/3 signalling pathway (29,30).…”

“…Phosphorylation-activated TβR-I then combines with Smad2/3. Moreover, phosphorylation-activated Smad2/3 combines with Smad4 to form a protein polymer, which is transferred from the cytoplasm to the nucleus and regulates the transcription and expression of a variety of downstream target genes, including Col-I, Col-III and α-SMA ( 29-31 ). In a positive feedback mechanism, the protein complex acts on the promoter region of the TGFβ1 gene to promote its expression and TGFβ1 autocrine signalling.…”

Targeting Hepatic Stellate Cells for the Treatment of Liver Fibrosis by Natural Products: Is It the Dawning of a New Era?

“…Its antioxidant properties inhibit the activation of HSCs and regulate MMP-2, TIMP-2, and collagens. The pharmacological pathway was suggested to be TGFb/SMAD signaling (Yuan et al, 2018). Astragaloside I, a compound of the astragaloside family, was shown to proliferate inhibition on the HSC cell line LX-2 (Guo et al, 2018).…”