Protective effects of Ampelopsis brevipedunculata against in vitro hepatic stellate cells system and thioacetamide-induced liver fibrosis rat model

Pharm Biol. 2017 Dec;55(1):1577-1585. doi: 10.1080/13880209.2017.1311928.

Abstract

Context: Ampelopsis brevipedunculata Maxim (Vitaceae) is a traditional medicinal herb used for treating liver disorders.

Objective: The hepatoprotective effects of A. brevipedunculata ethanol extract (ABE) was investigated in experimental models of fibrosis.

Materials and methods: Hepatic stellate cells (HSCs) system in vitro and thioacetamide (TAA)-induced liver fibrosis rat model in vivo were used. Sprague-Dawley rats were divided into five groups of eight each (control, TAA, TAA with ABE 10 mg/kg, ABE 100 mg/kg and silymarin 50 mg/kg groups, respectively). Fibrosis was induced except to the control group by TAA (200 mg/kg, i.p.) twice per week for 13 weeks. ABE and silymarin was administered orally six times per week from the 7th week to the 13th week.

Results: In HSC-T6 cells, ABE (0.1 mg/mL) and silymarin (0.05 mg/mL) significantly (p < 0.01) induced apoptosis (12.94 ± 5.72% and 14.9 ± 3.8%, respectively) compared with control group (7.51 ± 1.26%). The expression of fibrosis related genes (TGF-β, α-SMA and Col1A1) in HSC-T6 cells were significantly (p < 0.01) downregulated in ABE-treated groups compared with control group. In in vivo studies, ABE (10 and 100 mg/kg) treatment ameliorated the altered levels of serum biomarkers significantly (p < 0.01 and p < 0.001) in TAA-induced groups. Further, ABE (10 and 100 mg/kg) significantly (p < 0.01) attenuated the altered histopathological findings, glutathione content and the accumulation of hydroxyproline.

Conclusion: These results collectively indicate that ABE can potentially be developed as a therapeutic agent in the treatment of hepatic fibrosis.

Keywords: Extracellular matrix; apoptosis; glutathione; hydroxyproline; reactive oxygen species; silymarin.

Publication types

  • Comparative Study

MeSH terms

  • Actins / genetics
  • Ampelopsis / chemistry*
  • Animals
  • Apoptosis / drug effects
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Hepatic Stellate Cells / drug effects*
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / genetics
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Silymarin / pharmacology
  • Thioacetamide / toxicity
  • Transforming Growth Factor beta / genetics

Substances

  • Actins
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Plant Extracts
  • Silymarin
  • Transforming Growth Factor beta
  • smooth muscle actin, rat
  • Thioacetamide