Induction of CYP1A by a diterpene quinone tanshinone IIA isolated from a medicinal herb Salvia miltiorrhiza in C57BL/6J but not in DBA/2J mice.
Effects of tanshinone IIA, an active diterpene quinone of the herbal medicine Salvia miltiorrhiza (Danshen), on cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutathione S-transferase (GST) were studied in the arylhydrocarbon (Ah)-responsive C57BL/6J (B6) and nonresponsive DBA/2J (D2) mice. Oral treatment of tanshinone IIA caused a dose-dependent increase of liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity in B6 but not in D2 mice. In B6 mice, tanshinone IIA increased hepatic benzo(a)pyrene hydroxylation (AHH), 7-ethoxyresorufin O-deethylation, MROD, and 7-ethoxycoumarin O-deethylation activities. The levels of Cyp1A2 protein and mRNA were elevated. On the contrary, in D2 mice, tanshinone IIA decreased hepatic AHH and nifedipine oxidation activities and the CYP3A protein level without affecting other activities determined. Cyp1A2 protein and mRNA levels were not affected by tanshinone IIA in D2 mice. Tanshinone IIA had no effects on UGT and GST activities in both B6 and D2 mice. These results demonstrated that induction of CYP1A2 by tanshinone IIA depended on the Ah-responsiveness and occurred at pre-translational level.
Ueng
Yune-Fang
YF
National Research Institute of Chinese Medicine, 155-1, Li-Nong Street, Sec. 2, Taipei 112, Taiwan, ROC. ueng@cma23.nricm.edu.tw
Kuo
Ya-Hui
YH
Wang
Shu-Yun
SY
Lin
Yun-Lian
YL
Chen
Chieh-Fu
CF
D045784:Abietanes; D000284:Administration, Oral; D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013045:Species Specificity
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D012333:RNA, Messenger; C021751:tanshinone; D019388:Cytochrome P-450 CYP1A2; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase