About: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

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About: Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study
Creator	Li, Jianan Zhou, Shu-Feng Bei, Yu Chang, Cui He, Zhi-Xu Huang, Yadong Luo, Rong Pang, Jiyan Su, Junhui Su, Zhijian Xiang, Qi Xu, Jinmei Yang, Hongtu Yang, Lun Zhang, Minjing Zhang, Qihao Zhou, Zhi-Wei
Source	PMC
abstract	Natural compounds are becoming popular for the treatment of illnesses and health promotion, but the mechanisms of action and safety profiles are often unknown. Xyloketal B (XKB) is a novel marine compound isolated from the mangrove fungus Xylaria sp., with potent antioxidative, neuroprotective, and cardioprotective effects. However, its molecular targets and effects on drug-metabolizing enzymes are unknown. This study aimed to investigate the potential molecular targets of XKB using bioinformatic approaches and to examine the effect of XKB on the expression and activity of rat cytochrome P450 3a (Cyp3a) subfamily members using midazolam as a model probe. DDI-CPI, a server that can predict drug–drug interactions via the chemical–protein interactome, was employed to predict the targets of XKB, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze the pathways of the predicted targets of XKB. Homology modeling was performed using the Discovery Studio program 3.1. The activity and expression of rat hepatic Cyp3a were examined after the rats were treated with XKB at 7 and 14 mg/kg for 8 consecutive days. Rat plasma concentrations of midazolam and its metabolite 1′-OH-midazolam were determined using a validated high-performance liquid chromatographic method. Bioinformatic analysis showed that there were over 324 functional proteins and 61 related signaling pathways that were potentially regulated by XKB. A molecular docking study showed that XKB bound to the active site of human cytochrome P450 3A4 and rat Cyp3a2 homology model via the formation of hydrogen bonds. The in vivo study showed that oral administration of XKB at 14 mg/kg to rats for 8 days significantly increased the area under the plasma concentration-time curve (AUC) of midazolam, with a concomitant decrease in the plasma clearance and AUC ratio of 1′-OH-midazolam over midazolam. Further, oral administration of 14 mg/kg XKB for 8 days markedly reduced the activity and expression of hepatic Cyp3a in rats. Taken together, the results show that XKB could regulate networks of molecular proteins and related signaling pathways and that XKB downregulated hepatic Cyp3a in rats. XKB might cause drug interactions through modulation of the activity and expression of Cyp3a members. More studies are warranted to confirm the mechanisms of action of XKB and to investigate the underlying mechanism for the regulating effect of XKB on Cyp3a subfamily members.
has issue date	2014-12-12(xsd:dateTime)
bibo:doi	10.2147/dddt.s73476
bibo:pmid	25548518
has license	cc-by-nc
sha1sum (hex)	5e8abc62533a447422d5ead64d4ae4991cc99052
schema:url	https://doi.org/10.2147/dddt.s73476
resource representing a document's title	Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study
has PubMed Central identifier	PMC4271727
has PubMed identifier	25548518
schema:publication	Drug Des Devel Ther
resource representing a document's body	covid:5e8abc62533a447422d5ead64d4ae4991cc99052#body_text
is schema:about of	covid:arg/5e8abc62533a447422d5ead64d4ae4991cc99052 named entity 'Rat' named entity '8 days' named entity 'Bioinformatic analysis' named entity 'Cyp3a' named entity 'Cyp3a' named entity 'plasma' named entity 'downregulated' named entity 'XKB' named entity 'XKB' named entity 'rat' named entity 'hydrogen bonds' named entity 'midazolam' named entity 'hepatic' named entity 'XKB' named entity 'molecular docking' named entity 'rat' named entity 'substrate' named entity 'mRNA' named entity 'receptor' named entity 'XKB' named entity 'free radical' named entity 'rat' named entity 'SIRT5' named entity 'PRDX2' named entity 'biosynthetic' named entity 'GTP' named entity 'ADMET' named entity 'XKB' named entity 'hepatocyte' named entity 'XKB' named entity 'active site' named entity 'elimination half-life' named entity 'NR1I2' named entity 'midazolam' named entity 'receptor molecules' named entity 'bradykinin' named entity 'iron' named entity 'midazolam' named entity 'substrate' named entity 'epithelial cell' named entity 'phosphodiesterase 4B' named entity 'tyrosine kinase receptor' named entity 'CYP3A4' named entity 'XKB' named entity 'signaling pathways' named entity 'midazolam' named entity 'metabolite' named entity 'AUC' named entity 'analyte' named entity 'conjugation' named entity 'CYPs' named entity 'progestins' named entity 'midazolam' named entity 'AUC' named entity 'rat' named entity 'XKB' named entity 'chemokine receptor' named entity 'receptor' named entity 'therapeutic effect' named entity 'homology modeling' named entity 'sequence similarity' named entity 'methionine' named entity 'physiological' named entity 'endothelial'

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