Proteomic Investigations of Transcription Factors Critical in Geniposide-Mediated Suppression of Alcoholic Steatosis and in Overdose-Induced Hepatotoxicity on Liver in Rats

摘要

Alcoholic steatosis is one of the most prevalent forms of liver disease, and appropriate insight and application of anti-steatosis drugs must be considered. Geniposide, the major active constituent of the Gardenia jasminoides (Ellis) fruit, has been commonly used as a traditional herbal medicine for the treatment of liver diseases. However, its hepatoprotective effect on alcoholic steatosis has not been reported. Moreover, geniposide overdose-induced hepatotoxicity was demonstrated. Hence, its therapeutic effects and overdo-seinduced hepatotoxicity in rat models along with corresponding targets, especially the targets of transcription factors (TFs), were systematically investigated in this study by using a concatenated tandem array of consensus TF response elements. The results indicate that geniposide can attenuate alcoholic steatosis and liver injury by enhancing the transcriptional activities of peroxisome proliferator-activated receptor-alpha and hepatocyte nuclear factors 1 alpha and 4 alpha, while geniposide overdose perturbs other TFs. In addition, therapeutic doses and overdoses of geniposide have differentiated target TFs. This study is the first to provide a systematic insight into the difference of critical transcription factors between the actions of therapeutic doses and overdoses of geniposide, as well as much-needed attention to the important topic of alcoholic liver disease therapy.