Open AccessChlorogenic acid inhibits cholestatic liver injury induced by α‐naphthylisothiocyanate: involvement of STAT 3 and NF κB signalling regulation
Author(s) -
Tan Zhen,
Luo Min,
Yang Julin,
Cheng Yuqing,
Huang Jing,
Lu Caide,
Song Danjun,
Ye Meiling,
Dai Manyun,
Gonzalez Frank J.,
Liu Aiming,
Guo Bin
Publication year - 2016
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12592
Subject(s) - liver injury , signalling , chlorogenic acid , chemistry , hedgehog signaling pathway , signalling pathways , stat3 , pharmacology , signal transduction , biochemistry , medicine , biology , microbiology and biotechnology , food science
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 ɑ‐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‐α 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 κB. Conclusions These data suggest that CGA inhibits both ANIT ‐induced intrahepatic cholestasis and the liver injury. This protective effect involves down‐regulation of STAT 3 and NF κB signalling.