{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:36:04Z","timestamp":1786725364823,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>Cytochrome P450 2C8 (CYP2C8) is known to cause drug interactions via pharmacokinetic alterations of drugs, but it\u2019s also explicitly crucial for endogenous metabolism, like the generation of epoxyeicosatrienoic acids (EETs) from arachidonic acid. CYP2C8 expression is reported to be altered in various cancers, where CYP2C8\u2010mediated EETs promote tumorigenesis. Conversely, thymoquinone, an extensively used complementary medicine, has emerged as a promising candidate against cancer due to its ability to curb tumorigenesis. Nevertheless, to date, limited information is available about the impact of thymoquinone on CYP2C8 inhibition. Therefore, we planned to explore the same using in silico, in vitro, and in vivo approaches. The current results reveal the followings: (a) thymoquinone could markedly inhibit CYP2C8 based on study using amodiaquine N\u2010deethylation in human liver microsomes (HLM); (b) thymoquinone could strongly interact with the active site of the human CYP2C8 as demonstrated by molecular docking analysis; (c) thymoquinone could restrict the metabolic depletion of repaglinide (a CYP2C8 substrate) in rat liver microsomes; (d) thymoquinone altered the pharmacokinetic profile of repaglinide (a CYP2C8 substrate) in rats, resulting in repaglinide\u02b9s increased systemic exposure and reduced clearance; (e) thymoquinone could retard EET\u2019s formation in HLM. Further studies are warranted to evaluate the biological significance of thymoquinone\u2010mediated modulation of the CYP2C8\/EET axis in relevant cancer models.<\/jats:p>","DOI":"10.1002\/cbic.202600003","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:12:01Z","timestamp":1785957121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Thymoquinone as an Inhibitor of CYP2C8\/EET Axis"],"prefix":"10.1002","volume":"27","author":[{"given":"Sumit","family":"Dhiman","sequence":"first","affiliation":[{"name":"Pharmacology Division CSIR\u2010Indian Institute of Integrative Medicine  Jammu 180001 India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad 201002 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Manhas","sequence":"additional","affiliation":[{"name":"Pharmacology Division CSIR\u2010Indian 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