Codonopis bulleynana Forest ex Diels (cbFeD) effectively attenuates hepatic fibrosis in CCl4-induced fibrotic mice model

Biomed Pharmacother. 2021 Jan:133:110960. doi: 10.1016/j.biopha.2020.110960. Epub 2020 Nov 13.

Abstract

The root of Codonopis bulleynana Forest ex Diels (cbFeD), a tonic food widely used in Yunnan Province of China, was found to have a wide range of pharmacological effects. The present study was designed to investigate the anti-fibrotic effect of water extracts of cbFeD in chronic liver injury mice model induced by carbon tetrachloride (CCl4) and to explore its underlying mechanisms. Phytochemical analysis revealed multiple components were present in the water extract of cbFeD and the compounds were mostly enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc. Treatment with cbFeD significantly attenuated liver injury and fibrosis in CCl4-administered mice evidenced by improved liver histology, ameliorated apoptosis of hepatocytes, and decreased transaminase levels in the serum. Decreased activities of superoxide dismutase (SOD) and catalase (CAT) were markedly reversed upon treatment with cbFeD while levels of malondialdehyde (MDA) and glutathione (GSH) were significantly restored towards normal values. cbFeD also suppressed intrahepatic inflammatory cell infiltration and Kupffer cell activation. Furthermore, our study revealed an inhibitory effect of cbFeD on hepatic stellate cells (HSCs) activation both in vitro and in vivo. In conclusion, cbFeD could exert a protective role against liver fibrosis in mice model induced by CCl4 that is comparable to the positive control silymarin and might be developed into a promising anti-fibrotic drug.

Keywords: Codonopis bulleynana Forest ex Diels; Fibrogenesis; Hepatic stellate cell; Inflammation; Liver injury.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carbon Tetrachloride
  • Cell Line
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Chemotaxis, Leukocyte / drug effects
  • Codonopsis* / chemistry
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Kupffer Cells / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / pathology
  • Liver Cirrhosis, Experimental / prevention & control*
  • Macrophage Activation / drug effects
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots

Substances

  • Inflammation Mediators
  • Plant Extracts
  • Carbon Tetrachloride