Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats

Jin Chai, Xiaohuang Du, Sheng Chen, Xinchan Feng, Ying Cheng, Liangjun Zhang, Yu Gao, Shaoxue Li, Xiaochong He, Rongquan Wang, Xiangdong Zhou, Yong Yang, Weizao Luo, Wensheng Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)

Abstract

Background & aims: Oleanolic acid is abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb for the treatment of jaundice. However, the hepatoprotective role of oleanolic acid in obstructive cholestasis and its underlying molecular mechanism are unclear. Methods: Normal rats and bile duct-ligated (BDL) rats were given oleanolic acid and serum biochemistry, bile salts, and pro-inflammatory factors were measured, as well as the expression levels of liver bile acid synthesis and detoxification enzymes, membrane transporters, nuclear receptors, and transcriptional factors. Results: Oral administration of oleanolic acid at 100 mg/kg did not cause rat liver injury. However, it significantly reduced the serum levels of alanine aminotransferase (ALT) on days 7 and 14, aspartate aminotransferase (AST) and TNF-α on day 14, and alkaline phosphatase (ALP) and IL-1β on days 3, 7, and 14 in the BDL rats. Furthermore, the serum levels of total bile acid (TBA) and bile acids, including CDCA, CA, DCA, and Tα/βMCA were significantly reduced by oleanolic acid on day 3 in the BDL rats. In addition, the expression levels of detoxification enzymes Cyp3a, Ugt2b, Sult2a1, Gsta1-2, and Gstm1-3, membrane transporters Mrp3, Mrp4, Ostβ, Mdr1, Mdr2, and Bsep, nuclear receptors Pxr, Vdr, Hnf4α, Rxrα, Rarα, Lxr, and Lrh-1, and transcriptional factors Nrf2, Hnf3β, and Ahr were significantly increased in oleanolic acid-treated rats. Conclusion: We demonstrated that the oral administration of oleanolic acid attenuates liver injury, inflammation, and cholestasis in BDL rats. The anti-cholestatic effect may be associated with the induction of hepatic detoxification enzymes and efflux transporters mediated by nuclear receptors and transcriptional factors.
Original languageEnglish
Pages (from-to)1691-1702
Number of pages12
JournalInternational Journal of Clinical and Experimental Medicine
Volume8
Issue number2
Publication statusPublished - 28 Feb 2015
Externally publishedYes

Keywords

  • Detoxification enzyme
  • Hepatic efflux transporter
  • Nuclear receptor
  • Obstructive cholestasis
  • Oleanolic acid
  • Synthetic enzyme
  • Transcriptional factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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