Differential induction of the expression of GST subunits by geniposide in rat hepatocytes.
Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has the biological capabilities of detoxication, antioxidation, and anticarcinogenesis. In this study, the mechanism of geniposide affecting the GST (glutathione S-transferase) system was investigated. Primary cultured rat hepatocytes were treated with geniposide and examined for total GST activity and expression of GST subunits. The results showed that the geniposide-induced GST activity was dose and time dependent. Western blotting data demonstrated that geniposide induced increased protein levels of GSTM1 and GSTM2 (approximately 1.7- and 1.8-fold of control, respectively), but did not increase those of GSTA1. The corresponding transcripts levels were confirmed by RT-PCR. Using PD98059, the effect of geniposide was verified to be via the MEK pathway. The results suggest that geniposide possesses a potential for detoxication by inducing GST activity via increasing the transcription of GSTM1 and GSTM2.
Kuo
Wu-Hsien
WH
Division of Gastroenterology, Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan.
Wang
Chau-Jong
CJ
Young
Shun-Chieh
SC
Sun
Yuan-Chang
YC
Chen
Yi-Jun
YJ
Chou
Fen-Pi
FP
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D004790:Enzyme Induction / Q000187:drug effects* / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D005638:Fruit; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006027:Glycosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006505:Hepatitis / Q000188:drug therapy; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology*; D039823:Iridoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D010936:Plant Extracts; D011714:Pyrans; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019666:Rubiaceae; D013997:Time Factors
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D005982:Glutathione Transferase; D006027:Glycosides; D039823:Iridoids; D007527:Isoenzymes; D010936:Plant Extracts; D011714:Pyrans; D012333:RNA, Messenger; C007835:geniposide; C412602:glutathione S-transferase Mu 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one