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Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside
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Na LI1, 2, Jie SONG1, Xiao-fei LI2, Ya WANG2, Ya-kun MENG2, Can TU2, Chun-yu LI3, Zhi-jie MA2, Jing-yao PANG2, Rui-yu LI2, Xiao-he XIAO4, Ting-guo KANG1, *, Jia-bo WANG2, *
Acta Pharmaceutica Sinica | 2017, 52(7) : 1063 - 1068
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Acta Pharmaceutica Sinica | 2017, 52(7): 1063-1068
• SPECIAL REPORTS Herb-Induced Liver Injury and Safe Usage •
Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside
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Na LI1, 2, Jie SONG1, Xiao-fei LI2, Ya WANG2, Ya-kun MENG2, Can TU2, Chun-yu LI3, Zhi-jie MA2, Jing-yao PANG2, Rui-yu LI2, Xiao-he XIAO4, Ting-guo KANG1, *, Jia-bo WANG2, *
Affiliations
  • 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
Published: 2017-07-12 doi: 10.16438/j.0513-4870.2017-0392
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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.

Polygonum multiflorum  /  trans-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside  /  liver injury  /  metabolic factors  /  phaseⅠ metabolism  /  phase Ⅱ metabolism
Na LI, Jie SONG, Xiao-fei LI, Ya WANG, Ya-kun MENG, Can TU, Chun-yu LI, Zhi-jie MA, Jing-yao PANG, Rui-yu LI, Xiao-he XIAO, Ting-guo KANG, Jia-bo WANG. Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside[J]. Acta Pharmaceutica Sinica, 2017 , 52 (7) : 1063 -1068 . DOI: 10.16438/j.0513-4870.2017-0392
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Year 2017 volume 52 Issue 7
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Article Info
doi: 10.16438/j.0513-4870.2017-0392
  • Receive Date：2017-04-20
  • Online Date：2026-01-14
  • Published：2017-07-12
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History
  • Received：2017-04-20
  • Revised：2017-06-13
Funding
Affiliations
    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
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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