Naringenin is a Potential Immunomodulator for Inhibiting Liver Fibrosis by Inhibiting the cGAS-STING Pathway  

作　　者：Li Chen Siwei Xia Shuqi Wang Yuanyuan Zhou Feixia Wang Zhanghao Li Yang Li Desong Kong Zili Zhang Jiangjuan Shao Xuefen Xu Feng Zhang Shizhong Zheng 

机构地区：[1]Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,Jiangsu,China [2]Chinese Medicine Modernization and Big Data Research Center,Nanjing University of Chinese Medicine,Nanjing,Jiangsu,China

出　　处：《Journal of Clinical and Translational Hepatology》2023年第1期26-37,共12页临床与转化肝病杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (82073914 and 81870423);the Jiangsu Province Traditional Chinese Medicine Science and Technology Development Plan Project (QN202112);the Joint Project of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica and Yangtze River Pharmaceutical (JKLPSE202005).

摘　　要：Background and Aims:Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease.The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.Methods:The relationship between the cGAS-stimulator of interferon genes(STING)pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database.Histopathology,immunohistochemistry,fluorescence staining,Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers.Molecular docking was performed to evaluate the relationship between naringenin and cGAS,and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.Results:Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease.Naringenin ameliorated liver injury and liver fibrosis,decreased collagen deposition and cGAS expression,and inhibited inflammation in carbon tetrachloride(CCl4)-treated mice.Molecular docking found that cGAS may be a direct target of naringenin.Consistent with the in vivo results,we verified the inhibitory effect of naringenin on activated hepatic stellate cells(HSCs).By using the cGAS-specific agonist double-stranded(ds)DNA,we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA.We verified that naringenin inhibited the cGAS-STING pathway,thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.Conclusions:Interrupting the cGAS-STING pathway helped reverse the fibrosis process.Naringenin has potential as an antihepatic fibrosis drug.

关 键 词：Liver fibrosis cGAS NARINGENIN INFLAMMATION Hepatic stellate cells 

分 类 号：R575[医药卫生—消化系统]