Chlorogenic acid inhibits cholestatic liver injury induced by α-naphthylisothiocyanate: involvement of STAT3 and NFκB signalling regulation

Author:

Tan Zhen1,Luo Min2,Yang Julin3,Cheng Yuqing1,Huang Jing2,Lu Caide2,Song Danjun2,Ye Meiling1,Dai Manyun2,Gonzalez Frank J4,Liu Aiming2,Guo Bin1

Affiliation:

1. Key Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, China

2. Medical School of Ningbo University, Ningbo, China

3. Ningbo College of Health Sciences, Ningbo, China

4. Laboratory of Metabolism, National Cancer Institute, NIH, Bethesda, MD, USA

Abstract

Abstract 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 NFκB. Conclusions These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves down-regulation of STAT3 and NFκB signalling.

Funder

National Natural Science Foundation of China

Zhejiang Provincial Education Department

Foundation for University Young Key Teacher by the Education Department of Hunan Province

Construct Program of the Key Discipline in Hunan Province

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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