Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats. |
| Authors: |
Chai, Jin Du, Xiaohuang Chen, Sheng Feng, XinChan Cheng, Ying Zhang, Liangjun Gao, Yu Li, Shaoxue He, Xiaochong Wang, Rongquan Zhou, Xiangdong Yang, Yong Luo, Weizao Chen, Wensheng
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| Citation: |
Chai J, etal., Int J Clin Exp Med. 2015 Feb 15;8(2):1691-702. eCollection 2015. |
| RGD ID: |
14701043 |
| Pubmed: |
PMID:25932098 (View Abstract at PubMed) |
| PMCID: |
PMC4402745 (View Article at PubMed Central) |
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.
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| Genes (Rattus norvegicus) |
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| Gstm1 (glutathione S-transferase mu 1) |
| Genes (Mus musculus) |
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| Gstm1 (glutathione S-transferase, mu 1) |
| Genes (Homo sapiens) |
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| GSTM1 (glutathione S-transferase mu 1) |
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