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Studies on the metabolism of a triptolide derivative (5R)-5-hydroxytriptolide in vitro
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Ye XU1, 2, Jiang-bo DU1, Hui-jin FENG1, Jian-ping ZUO1, Hong-tao XU1, *, Yuan-chao LI1, *, Da-fang ZHONG1, 2, *
Acta Pharmaceutica Sinica | 2019, 54(8) : 1484 - 1492
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Acta Pharmaceutica Sinica | 2019, 54(8): 1484-1492
• Original Articles •
Studies on the metabolism of a triptolide derivative (5R)-5-hydroxytriptolide in vitro
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Ye XU1, 2, Jiang-bo DU1, Hui-jin FENG1, Jian-ping ZUO1, Hong-tao XU1, *, Yuan-chao LI1, *, Da-fang ZHONG1, 2, *
Affiliations
  • 1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • 2. University of Chinese Academy of Sciences, Beijing 100049, China
Published: 2019-08-12 doi: 10.16438/j.0513-4870.2019-0327
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The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species:oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1-M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12, 13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.

(5R)-5-hydroxytriptolide  /  metabolism  /  metabolite confirmation  /  hepatocytes  /  liver microsomes
Ye XU, Jiang-bo DU, Hui-jin FENG, Jian-ping ZUO, Hong-tao XU, Yuan-chao LI, Da-fang ZHONG. Studies on the metabolism of a triptolide derivative (5R)-5-hydroxytriptolide in vitro[J]. Acta Pharmaceutica Sinica, 2019 , 54 (8) : 1484 -1492 . DOI: 10.16438/j.0513-4870.2019-0327
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Year 2019 volume 54 Issue 8
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Article Info
doi: 10.16438/j.0513-4870.2019-0327
  • Receive Date：2019-04-24
  • Online Date：2026-01-26
  • Published：2019-08-12
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History
  • Received：2019-04-24
  • Revised：2019-06-03
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    1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    2. University of Chinese Academy of Sciences, Beijing 100049, 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
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Genus		 种数
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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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