Enzyme kinetic and molecular docking studies on the metabolic interactions of 1-hydroxy-2,3,5-trimethoxy-xanthone, isolated from Halenia elliptica D. Don, with model probe substrates of human cytochrome P450 enzymes

Ren, Feng; Zhou, Xuelin; Or, Penelope M.Y.; Yi, Jun; Tan, Xiang Shan; Fu, Jie; Ma, Chao; Shi, Jian; Tao, Chun; Wang, Yan; Yeung, John H.K.

doi:10.1016/j.phymed.2012.06.009

Cited by 17 publications

(9 citation statements)

References 29 publications

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“…3c and d). As calculated from Ki and αKi values, the α value (α¼0.94) was approximately equal to 1 which further confirmed that the inhibition was competitive (Feng et al, 2012;Shou et al, 2000). The IC 50 value of the positive control ketoconazole on rat CYP3A2 was 1.1 μM (0.59 μg/ml) with MDZ (50 mM) as the substrate (Fig.…”

Section: Enzymatic Kinetic Study For Rat Cyp3a2 Inhibitionsupporting

confidence: 56%

“…Graphical inspections from Primary Lineweaver-Burk plot, Dixon plot and Secondary Lineweaver-Burk plot were used to illustrate the inhibition types, Ki and αKi values (Feng et al, 2012;Shou et al, 2001). Pharmacokinetic parameters of ATV, including half-life (t 1/2α and t 1/2β ), maximum drug concentration (C max ), area under curve (AUC 0-t and AUC 0-1 ), clearance (CL), and mean retention time (MRT 0-t and MRT 0-1 ), were calculated using a two-compartmental model with DAS 2.0 pharmacokinetic software (Anhui Provincial Center for Drug Clinical Evaluation, Hefei, China).…”

Section: Discussionmentioning

confidence: 99%

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Herb–drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo

Cheng

Zhou

Wang

et al. 2015

Journal of Ethnopharmacology

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Section: Enzymatic Kinetic Study For Rat Cyp3a2 Inhibitionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Herb–drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo

Cheng

Zhou

Wang

et al. 2015

Journal of Ethnopharmacology

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“…The results herein were similar to those in human liver microsomes (HLMs). In the previous study (Feng et al ., ), with HLMs, HM‐1 showed moderate inhibitory effects on CYP1A2 (IC 50 = 1.06 μ m ) and CYP2C9 (IC 50 = 3.89 μ m ), and slight inhibition of CYP3A4 (IC 20 = 11.94 μ m ).…”

Section: Resultsmentioning

confidence: 94%

“…Previous literature found that xanthone derivatives from mangosteen extract inhibited the metabolism of CYP2C9 and CYP3A4 substrates in both competitive and linear‐mixed inhibition manners, while the inhibition mode of CYP1A2 was linear‐mixed (Foti et al ., ). Our previous study reported the abundant component of H. elliptica , HM‐1, could inhibit CYP1A2, CYP2C9 and CYP3A4 (Feng et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Interaction effects on cytochrome P450 both in vitro and in vivo studies by two major bioactive xanthones from Halenia elliptica D. Don

Ren

Tan

Wen

et al. 2016

Biomedical Chromatography

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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.

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“…[ 30 ] 1-hydroxyl-2,3,5-trimethoxyxanthone revealed moderate inhibitory effects on CYP1A2 (IC 50 = 1.06 μm) and CYP2C9 (IC 50 = 3.89 μm), minimal inhibition on CYP3A4 (IC 50 = 11.94 μM), and no inhibition on CYP2D6 (dextromethorphan) and probe substrates CYP2E1 (chlorzoxazone). [ 31 ] In vitro metabolic transformations of five xanthones of H. elliptica have been evaluated by metabolic transformation in rat liver microsomes in vitro . The results showed that the metabolic transformation occurred mainly at 2-, 4-, 5-, and 7-carbonic positions on their structures.…”

Section: Phytochmistry Researchmentioning

confidence: 99%

Ethnopharmacological, chemical, and pharmacological aspects of Halenia elliptica: A comprehensive review

et al. 2015

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Traditional Tibetan medicine (TTM) is an old traditional medical system, which is an effective and natural method of improving physical and mental health, and has been widely spread in the western part of China for centuries. Halenia elliptica (H. elliptica) D. Don, known as “Jiadiranguo” (Tibetan medicine name) is one of the most important herbal medicine in TTM that is from the genus Halenia (family: Gentianaceae). The whole herb can be used as a medicine to treat hepatobiliary diseases and xeransis, and possesses many biological and pharmacological activities including heat clearing, bile benefiting, liver soothing, digestion promoting, blood nursing, detoxification activities, and so on. In modern research, H. elliptica can be used to treat acute or chronic hepatitis, especially hepatitis B. In addition, the chemical compounds of the herb have potent antihepatitis B virus (anti-HBV) activity in vitro. As an important TTM, further studies on H. elliptica can lead to the development of new drugs and therapeutics for various diseases, and more attention should be paid on the aspects of how to utilize it better.

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Enzyme kinetic and molecular docking studies on the metabolic interactions of 1-hydroxy-2,3,5-trimethoxy-xanthone, isolated from Halenia elliptica D. Don, with model probe substrates of human cytochrome P450 enzymes

Cited by 17 publications

References 29 publications

Herb–drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo

Herb–drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo

Interaction effects on cytochrome P450 both in vitro and in vivo studies by two major bioactive xanthones from Halenia elliptica D. Don

Ethnopharmacological, chemical, and pharmacological aspects of Halenia elliptica: A comprehensive review

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