Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 68, Issue 9, Pages 1203-1213Publisher
WILEY
DOI: 10.1111/jphp.12592
Keywords
chlorogenic acid; cholestasis; NF kappa B; STAT3; alpha-naphthylisothiocyanate
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Funding
- National Natural Science Foundation of China [81274178, 81273582, 81302848]
- Zhejiang Provincial Education Department [Y201329949]
- Foundation for University Young Key Teacher by the Education Department of Hunan Province
- Construct Program of the Key Discipline in Hunan Province
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Objectives Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury. Methods Twenty-five male 129/Sv mice were administered with CGA, and ANIT challenge was performed at 75 mg/kg on the 4th day. Blood was collected and subjected to biochemical analysis; the liver tissues were examined using histopathological analysis and signalling pathways. Key findings Chlorogenic acid almost totally attenuated the ANIT-induced liver damage and cholestasis, compared with the ANIT group. Dose of 50 mg/kg of CGA significantly prevented ANIT-induced changes in serum levels of alanine aminotransferase, alkaline phosphatases, total bile acid, direct bilirubin, indirect bilirubin (5.3-, 6.3-, 18.8-, 158-, 41.4-fold, P< 0.001) and aspartate aminotransferase (4.6-fold, P< 0.01). Expressions of the altered bile acid metabolism and transport-related genes were normalized by cotreatment with CGA. The expressions of interleukin 6, tumour necrosis factor-alpha and suppressor of cytokine signalling 3 were found to be significantly decreased (1.2-fold, ns; 11.0-fold, P< 0.01; 4.4-fold, P< 0.05) in the CGA/ANIT group. Western blot revealed that CGA inhibited the activation and expression of signal transducer and activator of transcription 3 and NF kappa B. Conclusions These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves downregulation of STAT3 and NF kappa B signalling.
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