Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside
10.16438/j.0513-4870.2017-0392
- VernacularTitle:药物代谢酶抑制剂对反式二苯乙烯苷所致肝损伤易感性的影响
- Author:
Na LI
1
;
Jie SONG
1
;
Xiao-fei LI
2
;
Ya WANG
2
;
Ya-kun MENG
2
;
Can TU
2
;
Chun-yu LI
3
;
Zhi-jie MA
2
;
Jing-yao PANG
2
;
Rui-yu LI
2
;
Xiao-he XIAO
4
;
Ting-guo KANG
1
;
Jia-bo WANG
2
Author Information
1. School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China
2. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
3. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China
4. Integrative Medical Center for Liver Diseases, 302 Military Hospital, Beijing 100039, China
- Publication Type:SPECIAL REPORTS
- Keywords:
Polygonum multiflorum;
trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside;
liver injury;
metabolic factors;
phase I metabolism;
phase II metabolism
- From:
Acta Pharmaceutica Sinica
2017;52(7):1063-1068
- CountryChina
- Language:Chinese
-
Abstract:
By using the drug metabolizing enzyme inhibitors, the effects of metabolic factors on potential liver injury induced by the main component, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(trans-SG), in Polygonum multiflorum was investigated. The main metabolic enzyme isoforms involved in trans-SG metabolism were also screened. The results showed that trans-SG at the dosage 31 mg·kg-1 did not cause liver injury; and the combination of trans-SG with the phase I metabolic enzyme inhibitor, 1-benzylimidazole (10 mg·kg-1), did not change the degree of liver injury(compared with LPS + trans-SG group, P > 0.05). However, the combination of trans-SG with phase II metabolic enzyme inhibitor, ketoconazole(35 mg·kg-1), significantly increased the degree of liver injury(compared with LPS + trans-SG group, P < 0.05). The phase I metabolites of trans-SG were not detected in human liver microsomes phase I metabolism system, while the phase II trans-SG metabolites were detected in recombinant human UGT isozymes phase II metabolism system. Six isoforms of uridine diphosphate glucuronate transferase(UGT)exhibited abilities to metabolize trans-SG and the order of metabolic ability was: UGT1A1 > UGT1A9 > UGT1A7 > UGT1A10 > UGT2B7 > UGT1A8. The results showed that trans-SG was mainly metabolized by UGT in phase II metabolism. The inhibition of drug metabolizing enzymes of phase II can increase the liver injury susceptibility of trans-SG, which provides a reference to the evaluation of susceptible factors and drug incompatibility research of Polygonum multiflorum.
