Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model

J Ethnopharmacol. 2017 May 23;204:58-66. doi: 10.1016/j.jep.2017.04.011. Epub 2017 Apr 14.

Abstract

Ethnopharmacological relevance: In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea.

Aim of the study: This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats.

Materials and methods: Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches.

Results: Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways.

Conclusions: The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down-regulation of NF-κB, AP-1, and TGF-β/Smad signaling, probably via interference with the HMGB1/TLR4 axis.

Keywords: Cholestasis; Herbal medicine; Polyphenol; Rosmarinic acid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Bile Ducts / surgery
  • Cholestasis / drug therapy*
  • Cholestasis / metabolism
  • Cholestasis / pathology
  • Collagen / metabolism
  • Connective Tissue Growth Factor / metabolism
  • Fibrosis
  • Lamiaceae*
  • Ligation
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • NF-kappa B / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats, Sprague-Dawley
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-kappa B
  • Plant Extracts
  • Smad2 Protein
  • Smad2 protein, rat
  • Smad3 Protein
  • Smad3 protein, rat
  • Transcription Factor AP-1
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • Collagen