{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T03:10:01Z","timestamp":1751425801653,"version":"3.41.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T00:00:00Z","timestamp":1521763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003200","name":"Kementerian Sains, Teknologi dan Inovasi","doi-asserted-by":"publisher","award":["02\u201002\u201010\u2010SF0077"],"award-info":[{"award-number":["02\u201002\u201010\u2010SF0077"]}],"id":[{"id":"10.13039\/501100003200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using<jats:italic>in vitro<\/jats:italic>biochemical assay and<jats:italic>in silico<\/jats:italic>models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC<jats:sub>50<\/jats:sub>values beyond 1000\u00a0\u03bcM, indicating very weak potential in inhibiting CYP2C9.<jats:italic>In silico<\/jats:italic>docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed\u2010type inhibition with IC<jats:sub>50<\/jats:sub>value of 32.23\u00a0\u03bcM and K<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>value of 30.80\u00a0\u03bcM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC<jats:sub>50<\/jats:sub>of 6.08\u00a0\u03bcM and K<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>of 1.16\u00a0\u03bcM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both<jats:italic>in vitro<\/jats:italic>enzyme assay and<jats:italic>in silico<\/jats:italic>modeling with order of potency being diacerein\/rhein &gt; various glucosamine\/chondroitin forms.<jats:italic>In vitro<\/jats:italic>\u2010<jats:italic>in vivo<\/jats:italic>extrapolation of inhibition kinetics (using 1 + [I]\/K<jats:sub><jats:italic>i<\/jats:italic><\/jats:sub>ratio) demonstrated negligible potential of diacerein to cause interaction<jats:italic>in vivo<\/jats:italic>, whereas rhein was predicted to cause<jats:italic>in vivo<\/jats:italic>interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.<\/jats:p>","DOI":"10.1002\/bdd.2127","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T03:46:35Z","timestamp":1519789595000},"page":"205-217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cytochrome P450 2C9\u2010natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from<i>in vitro<\/i>data"],"prefix":"10.1002","volume":"39","author":[{"given":"Boon Hooi","family":"Tan","sequence":"first","affiliation":[{"name":"Division of Applied Biomedical Sciences and Biotechnology International Medical University Bukit Jalil Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nafees","family":"Ahemad","sequence":"additional","affiliation":[{"name":"School of Pharmacy Monash University Malaysia Bandar Sunway Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Nottingham Malaysia Campus Semenyih Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-8241","authenticated-orcid":false,"given":"Uma Devi","family":"Palanisamy","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia Bandar Sunway Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iekhsan","family":"Othman","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia Bandar Sunway Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beow Chin","family":"Yiap","sequence":"additional","affiliation":[{"name":"School of Pharmacy 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