Berberine ameliorates the progression of primary sclerosing cholangitis by activating farnesoid X receptor

Cell Biochem Biophys. 2024 Jun;82(2):767-776. doi: 10.1007/s12013-024-01226-8. Epub 2024 Feb 8.

Abstract

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease characterized by biliary infiltration, hepatic fibrosis and bile duct destruction. To date, treatment options for PSC are very limited. Therefore, the current study is aimed to investigate the therapeutic potential of berberine (BBR) against PSC. The disease was induced by feeding the mice with 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC) for four weeks. The serum biochemistry and liver histology were analyzed. Furthermore, the expression of farnesoid X receptor (FXR) was also evaluated by real-time PCR. The results indicated that berberine prevents the progression of PSC by modulating the expression of FXR which ultimately regulates other genes (including Cyp7A1 and BSEP) thus maintaining bile acids homeostasis. Furthermore, the docking analysis showed that berberine interacts with the binding pocket of FXR to activate the protein thus acting as an FXR agonist. In conclusion, data indicate that berberine protects the liver from PSC-related injury. This effect might be due to the modulation of FXR activity.

Keywords: BSEP; Berberine; Cyp7A1; DDC; FXR; Primary Sclerosing Cholangitis.

MeSH terms

  • Animals
  • Berberine* / pharmacology
  • Berberine* / therapeutic use
  • Bile Acids and Salts / metabolism
  • Binding Sites
  • Cholangitis, Sclerosing* / drug therapy
  • Cholangitis, Sclerosing* / metabolism
  • Cholangitis, Sclerosing* / pathology
  • Cholesterol 7-alpha-Hydroxylase / genetics
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Disease Progression
  • Humans
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Pyridines
  • Receptors, Cytoplasmic and Nuclear* / agonists
  • Receptors, Cytoplasmic and Nuclear* / metabolism

Substances

  • Berberine
  • farnesoid X-activated receptor
  • Receptors, Cytoplasmic and Nuclear
  • Bile Acids and Salts
  • 3,5-diethoxycarbonyl-1,4-dihydrocollidine
  • Cholesterol 7-alpha-Hydroxylase
  • Pyridines