{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:09:45Z","timestamp":1789063785697,"version":"build-2803163510"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Technology and Health Care"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The management of type 2 diabetes mellitus (T2DM) using peroxisome proliferator-activated receptor gamma (PPAR-\u03b3) agonists is currently limited by the adverse effects of thiazolidinediones (TZDs), such as fluid retention and weight gain. This necessitates the search for safer natural alternatives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study applied an integrated multi-layer\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      pipeline to screen 19 isoflavonoids from the FooDB database against the PPAR-\u03b3 crystal structure (PDB: 3DZY). The workflow combined molecular docking (Glide SP), structural interaction fingerprint (SIFt) validation and density functional theory (DFT) for electronic characterization followed by ADMET profiling and prediction of PASS bioactivity. Molecular dynamics (MD) simulations (100\u2005ns) and MM-GBSA binding free energy calculations were performed to explore dynamic stability and thermodynamic affinity of the complex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genistin (FDB012221) and daidzin (FDB012225) were identified as lead candidates with docking score of \u221210.837 and \u221210.125\u2005kcal\/mol respectively. DFT analysis revealed that FDB012221has better kinetic stability with a large HOMO-LUMO gap of 7.80\u2005eV, in addition, it was identified as drug-like by ADMET profiling, showing 58% human intestinal absorption and PASS analysis predicted. Molecular dynamics (MD) simulations validated the stable complex formation and FDB012221retained consistent hydrogen bonds with HIS435 (91%) and LEU325 (94%)further, the MM-GBSA values were \u221260\u2005kcal\/mol indicating strong thermodynamic binding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      FDB012221 is a potent PPAR-\u03b3 agonist with high binding affinity, electronic stability and a favorable pharmacokinetic profile. This isoflavonoid is a potential natural scaffold for the development of safer therapies for T2DM and is recommended for further\n                      <jats:italic toggle=\"yes\">in-vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in-vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09287329261481865","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:38:16Z","timestamp":1788889096000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational identification of isoflavonoids as novel PPAR-\u03b3 agonists for the treatment of type 2 diabetes mellitus"],"prefix":"10.1177","author":[{"given":"Abdulkadir","family":"Abdu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossamaldeen","family":"Bakreys","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Alternative Medicine, Faculty of Pharmacy, Northern Borders University, Rafha, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israa","family":"Abdelrahim","sequence":"additional","affiliation":[{"name":"University of Medical Science and Technology, Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazin Aboobaida Abdalla","family":"Abdelaziz","sequence":"additional","affiliation":[{"name":"Raghavendra Institute of Pharmaceutical Education and Research (RIPER) Affiliated to JNT University, Anantapur, AP, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind A","family":"Rikabi","sequence":"additional","affiliation":[{"name":"Department of Clinical Practice, College of Pharmacy, Northern Border University, Rafha, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soliman S","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Department of Clinical Practice, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Eltaib","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Northern Border University, Rafha, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115734"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-96175-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph191912296"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-015-2080-z"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.10001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.119776"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111448"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010218"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1024\/0300-9831\/a000782"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.03.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2480"},{"key":"e_1_3_3_13_2","article-title":"In silico evaluation of Plumbago auriculata phytocompounds as dual inhibitors of \u03b1-glucosidase and \u03b1-amylase","author":"Abdu A","unstructured":"Abdu A, Abdelaziz MAA, Sagir S, et al. 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