ReferenceID 5889
Oleanolic acid alleviates ANIT-induced cholestatic liver injury by activating Fxr and Nrf2 pathways to ameliorate disordered bile acids homeostasis
Phytomedicine
Background: Cholestasis is a clinical syndrome with high incidence and few effective treatments. Oleanolic acid (OA) is a triterpenoid compound with anti-cholestatic effects. Studies using bile duct ligation or lithochol
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- Reference Id
- 5889
- Evidence Id
- 22479
- Core Evidence Id
- 22479
- Source Reference Id
- 5046
- Herb2 Reference Id
- HBREF005843
- Subject Paper Key
- HBIN037940_35605478
- Pubmed Id
- 35605478
- Doi
- 10.1016/j.phymed.2022.154173
- Paper Title
- Oleanolic acid alleviates ANIT-induced cholestatic liver injury by activating Fxr and Nrf2 pathways to ameliorate disordered bile acids homeostasis
- Paper Abstract
- Background: Cholestasis is a clinical syndrome with high incidence and few effective treatments. Oleanolic acid (OA) is a triterpenoid compound with anti-cholestatic effects. Studies using bile duct ligation or lithocholic acid modeling have shown that the alleviating effect of OA on cholerosis is related to the regulation of nuclear factor erythroid 2 related factor (Nrf2) or farnesoid X receptor (Fxr). Purpose: This study aims to investigate the underlying mechanism of OA against alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury based on Nrf2 and Fxr dual signaling pathways. Methods: The ANIT-induced rats model was used with or without OA treatment. Serum biochemical indexes, liver histopathological changes and glutathione level were examined. Bile acids (BAs) targeted metabolomics based on UHPLC-MS/MS were performed. siRNA, RT-qPCR and western blot analysis were used to prove the role of Fxr and Nrf2 pathway in OA's anti-cholestatic liver injury in vivo and in vitro. Results: OA significantly alleviated ANIT-induced liver injury in rats, reduced primary bile acids, accelerated metabolism of BAs and reduced the intrahepatic accumulation of BAs. The expressions of bile salt export pump (Bsep), Na+-taurocholic cotransport polypeptide (Ntcp), UDP-glucuronyl transferase 1a1 (Ugt1a1) and Fxr in rat liver were markedly up-regulated, the activation of Nrf2 was promoted, and the expression of cholesterol 7α-hydroxylase (Cyp7a1) was decreased after OA treatment. Moreover, Fxr or Nrf2 silencing attenuated the regulation of OA on BAs homeostasis related transporters and enzymes in rat primary hepatocytes. Conclusion: OA may regulate BAs-related transporters and metabolic enzymes by activating Fxr and Nrf2 pathways, thus alleviating the cholestatic liver injury induced by ANIT.
- Journal
- Phytomedicine
- Publish Year
- 2022
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cholerosis; Cholestasis; Alpha-naphthylisothiocyanate; Anti-cholestatic Liver Injury; Cholestatic Liver Injury
- Paper Title Cn
- Paper Title En
- Oleanolic acid alleviates ANIT-induced cholestatic liver injury by activating Fxr and Nrf2 pathways to ameliorate disordered bile acids homeostasis
- Bilingual Status
- semi_complete