{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:26:56Z","timestamp":1774272416575,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Agriculture and Rural Affairs of the People\u2019s Republic of China","award":["NK17-6"],"award-info":[{"award-number":["NK17-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Maclekarpine E is a minor alkaloid from Macleaya species with reported in vitro anti-inflammatory activity, but its in vivo metabolism remains unexplored. This study investigated the metabolic fate of maclekarpine E in rats and evaluated the potential pharmacological relevance of its metabolites. Maclekarpine E was orally administered to male Sprague-Dawley rats (250 mg\/kg). Plasma, urine and feces were collected and analyzed by UPLC-Q-TOF-MS\/MS. CYP phenotyping was performed using recombinant human enzymes. Molecular docking against ABCG2 and ABCC2 was conducted to assess potential interactions of all fecal compounds with these efflux transporters. Network pharmacology was employed to predict potential anti-ulcerative colitis-related targets of the metabolites, generating hypotheses for future experimental validation. Nineteen phase I metabolites were identified. Biotransformations included ring-opening, demethylation and oxidation. All 19 metabolites were detected in feces, nine in plasma and two in urine. No phase II conjugates were observed. CYP2C19 was the only significantly active isoform under the tested conditions, mediating approximately 16.5% substrate depletion (p &lt; 0.05). All 20 fecal compounds bound ABCG2 (\u0394G &lt; \u22125.0 kcal\/mol); 19 bound ABCC2. Network pharmacology yielded 57 overlapping targets with ulcerative colitis, enriched in PI3K-Akt and MAPK pathways. This study provides the first comprehensive metabolic profile of maclekarpine E in rats. The compound undergoes CYP2C19-mediated oxidation and is predominantly excreted into feces. Its fecal metabolites are potential ABCG2\/ABCC2 substrates and may target UC-associated pathways based on network pharmacology predictions, warranting further experimental validation.<\/jats:p>","DOI":"10.3390\/cimb48030335","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:59:36Z","timestamp":1774267176000},"page":"335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biotransformation of Maclekarpine E in Rats: CYP2C19-Mediated Metabolism, Fecal Enrichment, and Network Pharmacology-Based Anti-Ulcerative Colitis Prediction"],"prefix":"10.3390","volume":"48","author":[{"given":"Yingxue","family":"Yang","sequence":"first","affiliation":[{"name":"Hunan Province Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Centre of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Centre of Yuelushan Laboratory, Changsha 410128, China"},{"name":"Shiyan Key Laboratory of Biological Resources and Eco-Environmental Protection, College of Chemical and Environmental Engineering, Hanjiang Normal University, Shiyan 442000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaojiao","family":"Xue","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Centre of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-8541","authenticated-orcid":false,"given":"Zhen","family":"Dong","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Centre of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Centre of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/ptr.5952","article-title":"Medicinal Plants of the Genus Macleaya (Macleaya cordata, Macleaya microcarpa): A Review of Their Phytochemistry, Pharmacology, and Toxicology","volume":"32","author":"Lin","year":"2018","journal-title":"Phytother. 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