Ethanol extract of Pharbitis nil ameliorates liver fibrosis through regulation of the TGFβ1-SMAD2/3 pathway

J Ethnopharmacol. 2022 Aug 10:294:115370. doi: 10.1016/j.jep.2022.115370. Epub 2022 May 11.

Abstract

Ethnopharmacological relevance: Pharbitis nil (L.) Choisy is a medicinal herb, and herbal remedies based on its seeds have been used to treat of obesity and liver diseases, including fatty liver and liver cirrhosis in East Asia.

Aim of the study: Liver fibrosis is a major cause of morbidity and mortality in patients with chronic liver inflammation such as that caused by non-alcoholic steatohepatitis. However, no effective pharmaceutical treatment for liver fibrosis has been approved. In this study, we aimed to investigate that ethanol extract of pharbitis nil (PNE) alleviates the liver fibrosis.

Materials and methods: We studied the effects of PNE on two preclinical models. Six-week-old male C57BL/6 mice were intraperitoneally injected with CCl4 twice weekly for 6 weeks and then treated with 5 or 10 mg/kg PNE daily from week 3 for weeks. Secondly, mice were fed HFD for 41 weeks and at 35 weeks treated with 5 mg/kg PNE daily for the remaining 6 weeks. In addition, we examined the antifibrotic effects of PNE in primary mouse hepatic stellate cells and LX-2 cells.

Results: PNE treatment ameliorated hepatocyte necrosis, inflammation, and liver fibrosis in CCl4-treated mice and inhibited the progression of liver fibrosis in mice with HFD-induced fibrosis. PNE reduced the expressions of fibrosis markers and SMAD2/3 activations in mouse livers and in TGFβ1-treated primary mouse hepatic stellate and LX-2 cells CONCLUSIONS: This study demonstrates that PNE attenuates liver fibrosis by downregulating TGFβ1-induced SMAD2/3 activation.

Keywords: Hepatic stellate cell (HSC); Inflammation; Liver fibrosis; Non-alcoholic steatohepatitis (NASH); Pharbitis nil (L.) Choisy; Transforming growth factor beta1 (TGFβ1).

MeSH terms

  • Animals
  • Ethanol / pharmacology
  • Fibrosis
  • Hepatic Stellate Cells
  • Humans
  • Inflammation / pathology
  • Ipomoea nil* / metabolism
  • Liver / metabolism
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Plant Extracts
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta1
  • Ethanol