Herbal compound 861 prevents hepatic fibrosis by inhibiting the TGF-β1/Smad/SnoN pathway in bile duct-ligated rats

BMC Complement Altern Med. 2018 Feb 5;18(1):52. doi: 10.1186/s12906-018-2119-7.

Abstract

Background: This study was to evaluate the effects of herbal compound 861 (Cpd861) on ski-related novel protein N (SnoN) and transforming growth factor-β1 (TGF-β1) /Smad signaling in rats with bile duct ligation (BDL)-induced hepatic fibrosis, and to explore the mechanisms of Cpd861 on hepatic fibrosis.

Methods: Thirty Wistar male rats were randomly divided into three groups: sham operation, BDL, and Cpd861. To induce hepatic fibrosis, BDL and Cpd861 group rats underwent bile duct ligation. Cpd861 at 9 g/kg/d or an equal volume of normal saline was administered intragastrically for 28 days. Liver injury was assessed biochemically and histologically. Protein and mRNA changes for SnoN and TGF-β1/Smad signaling (TGF-β1, Smad2, phosphorylated Smad2 [p-Smad2], phosphorylated Smad3 [p-Smad3], fibronectin, and collagen III) were determined by Western blotting and quantitative real-time PCR.

Results: BDL rats treated with Cpd861 had significantly alleviated hepatic fibrosis compared to BDL rats not receiving Cpd861 treatment. Moreover, Cpd861 decreased the expression of fibrosis-associated proteins fibronectin and collagen III in liver tissue. Cpd861 administration increased the expression of SnoN protein, did not change SnoN mRNA level, and decreased TGF-β1, p-Smad2, and p-Smad3 protein expression compared to BDL without Cpd861 treatment.

Conclusions: Cpd861 attenuates hepatic fibrosis by increasing SnoN protein expression and inhibiting the TGF-β1/Smad signaling pathway.

Keywords: Hepatic fibrosis; Herbal compound 861; Ski-related novel protein N; TGF-β1.

MeSH terms

  • Animals
  • Bile Ducts / injuries
  • Bile Ducts / surgery
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Immunohistochemistry
  • Liver / chemistry
  • Liver / drug effects
  • Liver / metabolism
  • Liver Cirrhosis / metabolism*
  • Male
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Smad Proteins / analysis
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1 / analysis
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Drugs, Chinese Herbal
  • Nerve Tissue Proteins
  • Skil_v1 protein, rat
  • Smad Proteins
  • Transcription Factors
  • Transforming Growth Factor beta1
  • herbal compound 861