{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:25:55Z","timestamp":1783117555832,"version":"3.54.6"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia","award":["IFPIP: 1036-166-1443"],"award-info":[{"award-number":["IFPIP: 1036-166-1443"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Drug-metabolizing enzymes are either boosted or suppressed by diabetes mellitus. This research was designed to explore Fagonia cretica L. aerial parts\u2019 impact on CYP3A4 and UGT2B7 activity and their mRNA expression in diabetic rats. Fagonia cretica (F. cretica) dried powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, methanol, and water. The methanol extract and aqueous fraction presented the most significant potential to decrease the concentration of alpha-hydroxyl midazolam, with 176.0 \u00b1 0.85 mg\/Kg and 182.9 \u00b1 0.99 mg\/Kg, respectively, compared to the streptozotocin (STZ)-induced diabetic group, reflecting the inhibition in CYP3A4 activity. The fold change in mRNA expression of CYP3A4 was decreased significantly by the methanol extract, and the aqueous fraction of F. cretica estimated by 0.15 \u00b1 0.002 and 0.16 \u00b1 0.001, respectively, compared with the diabetic group. Morphine metabolism was significantly increased in rats treated with F. cretica methanol extract and its aqueous fraction, displaying 93.4 \u00b1 0.96 mg\/Kg and 96.4 \u00b1 1.27 mg\/Kg, respectively, compared with the metabolism of morphine in the diabetic group, which highlights the induction of UGT2B7 activity. The fold change in mRNA expression of UGT2B7 was significantly increased by the methanol extract and the aqueous fraction, estimated at 8.14 \u00b1 0.26 and 7.17 \u00b1 0.23 respectively, compared to the diabetic group. Phytochemical analysis was performed using high-performance liquid chromatography (HPLC), where the methanol extract showed more flavonoids and phenolic compounds compared to the aqueous fraction of F. cretica. The obtained results were further consolidated by molecular docking studies, where quercetin showed the best fitting within the active pocket of CYP3A4, followed by gallic acid, displaying free binding energies (\u2206G) of \u221230.83 and \u221223.12 kcal\/mol, respectively. Thus, F. cretica could serve as a complementary medicine with standard anti-diabetic therapy that can modulate the activity of the drug-metabolizing enzymes.<\/jats:p>","DOI":"10.3390\/antiox12010119","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T01:42:44Z","timestamp":1672796564000},"page":"119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Profiling and Investigation of the Modulatory Effect of Fagonia cretica L. Aerial Parts on Hepatic CYP3A4 and UGT2B7 Enzymes in Streptozotocin\u2014Induced Diabetic Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-3370","authenticated-orcid":false,"given":"Shahzad","family":"Kamran","sequence":"first","affiliation":[{"name":"Punjab University College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukhsana","family":"Anwar","sequence":"additional","affiliation":[{"name":"Punjab University College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afifa","family":"Noor","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ihsan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Punjab University College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-4881","authenticated-orcid":false,"given":"Alaa A.","family":"Bagalagel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M.","family":"Aldurdunji","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiqa","family":"Ishtiaq","sequence":"additional","affiliation":[{"name":"Punjab University College of Pharmacy, University of the Punjab, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","first-page":"2238","article-title":"In vitro effect of mitragynine (a major alkaloid of Mitragyna speciosa korth) on aminopyrine metabolism in rat hepatocytes","volume":"3","author":"Anwar","year":"2012","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_2","first-page":"187","article-title":"The detoxification enzyme systems","volume":"3","author":"Liska","year":"1998","journal-title":"Altern. Med. 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