title: Effects of tetrahydroberberine and tetrahydropalmatine on hepatic cytochrome P450 expression and their toxicity in mice.
abstract: The aim of this study was to investigate the effects of tetrahydroberberine (THB) and tetrahydropalmatine (THP) on the expression of mouse liver cytochrome P450s, and evaluate their liver toxicity in mice. Real-time polymerase chain reaction (PCR) and western blot analyses were used to analyze the expression of major P450 isoforms. Liver toxicity was evaluated by measuring serum biochemical parameters and performing histopathological analysis. The real-time PCR results showed that THB induced Cyp1a2 (1.66 ± 0.34 fold, P < 0.05), Cyp3a11 (1.57 ± 0.24 fold, P < 0.05), and Cyp2e1 (1.75 ± 0.97 fold, P < 0.05) mRNA expression, while THP inhibited Cyp1a2 (0.66 ± 0.12 fold, P < 0.05) mRNA expression. The western blot results confirmed that the expression of CYP1A2, CYP3A, and CYP2E1 proteins in the mouse liver was induced by THB, whereas that of CYP1A2 was inhibited by THP. Toxicological studies showed that THB (40 mg/kg, oral gavage) increased mouse serum aspartate transaminase and total bilirubin, and liver malondialdehyde levels, and induced liver edema. No obvious changes in serum and liver tissue biochemical parameters were found and no significant pathological changes were detected in liver tissues after THP administration. Our results provide more information on the toxicity of THB and THP, and their related drug-drug interactions.
authors.affiliation: School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Dujun
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Danjuan
authors.initials: D
authors.lastname: Sui
authors.affiliation: School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address: ywei@ujs.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001599:Berberine / Q000031:analogs & derivatives* / Q000633:toxicity; D001600:Berberine Alkaloids / Q000633:toxicity*; D001663:Bilirubin / Q000097:blood; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D008565:Membrane Proteins
chemical_list: D001219:Aspartate Aminotransferases; D001599:Berberine; D001600:Berberine Alkaloids; D001663:Bilirubin; D019388:Cytochrome P-450 CYP1A2; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D008315:Malondialdehyde; D012333:RNA, Messenger; C014215:tetrahydropalmatine; C000617651:cytochrome P-450 2E1, mouse; C000617645:cytochrome P-450 1A2, mouse; C004645:canadine; C496508:Cyp3a11 protein, mouse; D008565:Membrane Proteins
keywords: Cytochrome P450; Expression level; Tetrahydroberberine; Tetrahydropalmatine; Toxicity