{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:27:13Z","timestamp":1784752033626,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National University Development Project (Glocal University 30 project) at Jeonbuk National University in 2024"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As a part of our ongoing search for bioactive constituents of Artemisia capillaris, we isolated 4-O-caffeoyl-2-C-methyl-d-threonic acid (PPT-14). This is a rare caffeic acid ester derivative that is reported here for the first time in the Artemisia species, which is the third occurrence in any plant species worldwide. In this study, we evaluated the anti-diabetic potential of PPT-14 using in vitro and in silico approaches. PPT-14 demonstrated significant inhibitory activity against two crucial enzymes linked to diabetes progression and complications: protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR). These had IC50 values of 64.92 and 19.50 \u00b5M, respectively. Additionally, PPT-14 exhibited free radical scavenging activity with 2,2-diphenyl-2-picrylhydrazyl (IC50 14.46 \u00b5M). Molecular docking and 200 ns molecular dynamics simulations confirmed that there were stable binding interactions with the key residues of PTP1B and AR, highlighting strong affinity and dynamic stability. Pharmacokinetic analyses revealed favorable water solubility, adherence to Lipinski\u2019s Rule of Five, and minimal interactions with cytochrome P450 enzymes, indicating the drug-like potential of PPT-14. Toxicity studies confirmed its safety profile, showing no genotoxicity, hepatotoxicity, or significant toxicity risks, with an acceptable oral LD50 value of 2.984 mol\/kg. These findings suggest that PPT-14 could be a promising multitarget lead compound for ameliorating diabetes and its associated complications.<\/jats:p>","DOI":"10.3390\/ijms26031286","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:36:51Z","timestamp":1738557411000},"page":"1286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unveiling the Multitarget Potential of a Rare Caffeoyl Ester from Artemisia capillaris for Diabetes Mellitus: An Integrated In Vitro and In Silico Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3111-893X","authenticated-orcid":false,"given":"Md. Nurul","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7280-0654","authenticated-orcid":false,"given":"Manh Tuan","family":"Ha","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, College of Pharmacy, Daegu Catholic University, Gyeongbuk 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Sun","family":"Min","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, College of Pharmacy, Daegu Catholic University, Gyeongbuk 38430, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-8868","authenticated-orcid":false,"given":"Jae Sue","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9145-9594","authenticated-orcid":false,"given":"Hyun Ah","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., and Boyko, E.J. 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