[Effect of Tibetan medicine zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2].
To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
Xiang-Yang
XY
Li
Yong-Nian
YN
Liu
Yong-Ping
YP
Li
Jun-Bo
JB
Zhu
Xing-Chen
XC
Yao
Yong-Fang
YF
Li
Mei
M
Yang
Ming
M
Yuan
Xue-Ru
XR
Fan
Yue-Miao
YM
Yin
D000284:Administration, Oral; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism* / Q000652:urine; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008297:Male; D038861:Medicine, Tibetan Traditional; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000652:urine; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine; D014527:Uric Acid / Q000031:analogs & derivatives / Q000652:urine; D014970:Xanthines / Q000652:urine
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D014970:Xanthines; D014527:Uric Acid; C030530:1-methyluric acid; D002110:Caffeine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C541077:NAT2 protein, rat; C021183:1,7-dimethylxanthine