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Interaction effects on cytochrome P450 both in vitro and in vivo studies by two major bioactive xanthones from Halenia elliptica D. Don
Author(s) -
Feng Ru,
Tan XiangShan,
Wen BaoYing,
Shou JiaWen,
Fu Jie,
He ChiYu,
Zhao ZhenXiong,
Li XiaoYang,
Zhu HuiXin,
Zhu Ping,
Shi JianGong,
Che ChunTao,
Yeung John H. K.,
Zhang XianFeng,
Wang Yan
Publication year - 2016
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3771
Subject(s) - chemistry , in vivo , cyp1a2 , hydroxylation , cytochrome p450 , microsome , in vitro , demethylation , pharmacology , biochemistry , ethyl acetate , metabolism , enzyme , gene expression , dna methylation , microbiology and biotechnology , gene , biology , medicine
The major components, 1‐hydroxy‐2,3,5‐trimethoxy‐xanthone (HM‐1) and 1,5‐dihydroxy‐2,3‐dimethoxy‐xanthone (HM‐5) isolated from Halenia elliptica D. Don (Gentianaceae), could cause vasodilatation in rat coronary artery with different mechanisms. In this work, high‐performance liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry (LCMS‐IT‐TOF) was used to clarify the metabolic pathways, and CYP450 isoform involvement of HM‐1 and HM‐5 were also studied in rat. At the same time, in vivo inhibition effects of HM‐1 and ethyl acetate extracts from origin herb were studied. Three metabolites of HM‐5 were found in rat liver microsomes (RLMs); demethylation and hydroxylation were the major phase I metabolic reactions for HM‐5. Multiple CYP450s were involved in metabolism of HM‐1 and HM‐5. The inhibition study showed that HM‐5 inhibited Cyp1a2, 2c6 and 2d2 in RLMs. HM‐1 inhibited activities of Cyp1a2, Cyp2c6 and Cyp3a2. In vivo experiment demonstrated that both HM‐1 and ethyl acetate extracts could inhibit Cyp3a2 in rats. In conclusion, the metabolism of xanthones from the origin herb involved multiple CYP450 isoforms; in vitro , metabolism of HM‐5 was similar to that of its parent drug HM‐1, but their inhibition effects upon CYP450s were different; in vivo , Cyp3a2 could be inhibited by HM‐1 and ethyl acetate extracts.