Corydalis saxicola Bunting Total Alkaloids ameliorate diet-induced non-alcoholic steatohepatitis by regulating hepatic PI3K/Akt and TLR4/NF-κB pathways in mice

Biomed Pharmacother. 2022 Jul:151:113132. doi: 10.1016/j.biopha.2022.113132. Epub 2022 May 25.

Abstract

Corydalis saxicola Bunting (Yanhuanglian), distributed in Southwest China, is mainly used for treatment of hepatitis, oral mucosal erosion, conjunctivitis, dysentery, acute abdominal pain and hemorrhoids in the folk. Corydalis saxicola Bunting Total Alkaloids (CSBTA) are the active ingredients extracted from the root of C. saxicola bunting. Non-alcoholic steatohepatitis (NASH) is the hinge between steatosis and cirrhosis in the spectrum of Non-alcoholic fatty liver disease (NAFLD), which has become one of the most common chronic liver diseases in the world. CSBTA can reduce tumors and brain diseases through anti-inflammatory and antioxidant pathways. Our study was designed to clarify the effects of CSBTA on the HFHC (High fat and high carbohydrate drinking) diet induced mice. In our research, A HFHC diet induced NASH mice model was applied to investigate the effects of CSBTA in vivo and obeticholic acid (OA) was set as positive control. Moreover, the underlying mechanisms were explored by palmitic acid (PA) and lipopolysaccharide (LPS) stimulated HepG2 cells in vitro. The in vivo study illustrated that CSBTA could alleviate mice away from the onset of NASH, and reduce intrahepatocellular lipid accumulation and hepatocyte inflammation under high fat condition. Further in vitro analysis confirmed that CSBTA attenuated inflammation and hepatic lipid accumulation by improving hepatic PI3K/Akt and suppressing hepatic TLR4/NF-κB pathways. In summary, this study demonstrated that CSBTA might be a promising compound for the treatment of NAFLD.

Keywords: Corydalis saxicola Bunting Total Alkaloids; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; PI3K/Akt and TLR4/NF-κB pathways.

MeSH terms

  • Alkaloids* / metabolism
  • Alkaloids* / pharmacology
  • Alkaloids* / therapeutic use
  • Animals
  • Corydalis* / metabolism
  • Diet
  • Inflammation / metabolism
  • Lipids / pharmacology
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • Alkaloids
  • Lipids
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Proto-Oncogene Proteins c-akt