{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:14:39Z","timestamp":1785446079774,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Imam Mohammad Ibn Saud Islamic University","award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}]},{"award":["IMSIU-DDRSP2601"],"award-info":[{"award-number":["IMSIU-DDRSP2601"]}],"id":[{"id":"https:\/\/ror.org\/05gxjyb39","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Diabetes mellitus is a growing health concern that causes numerous complications. Glycation produces advanced glycation end-products (AGEs), which promote diabetic complications. Targeting glycation is a strategy for combating the progression of diabetic complications. Pioglitazone enhances insulin sensitivity in patients with type 2 diabetes mellitus, but its impact on glycation remains unclear. This study aims to evaluate whether pioglitazone can inhibit glucose-induced glycation of human serum albumin (HSA), using in vitro assays and in silico tools. Pioglitazone inhibited &gt;70% of early glycation products and &gt;75% of AGEs. The treatment also reduced free lysine modification and improved biochemical markers, including carbonyl and free thiol levels. Pioglitazone exhibited moderate binding affinity for HSA, with a binding constant of 104 M\u22121. The interaction between pioglitazone and HSA was both spontaneous and entropically favourable. Molecular dynamics simulations revealed that the HSA\u2013pioglitazone complex remained quite stable, with RMSF, RMSD, SASA, Rg, and HSA\u2019s secondary structure showing minimal changes throughout the simulation. The overall binding energy for HSA\u2013pioglitazone complex formation was \u221230.06 \u00b1 0.31 kcal mol\u22121, as obtained from MD simulations. The findings suggest that pioglitazone likely interacts with glycation-prone regions of HSA, as indicated by spectroscopic and docking analyses, and contributes to the reduction of glycation.<\/jats:p>","DOI":"10.3390\/molecules31091519","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:15:02Z","timestamp":1777853702000},"page":"1519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Glucose-Induced Glycation of HSA by Pioglitazone: Multi-Spectroscopic and Bioinformatic Evidence"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5214-3204","authenticated-orcid":false,"given":"Jihad","family":"Alrehaili","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 4233-13317, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-1951","authenticated-orcid":false,"given":"Razique","family":"Anwer","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 4233-13317, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"ref_1","first-page":"1280","article-title":"Evaluation of Glycated Albumin and Microalbuminuria as Early Risk Markers of Nephropathy in Type 2 Diabetes Mellitus","volume":"7","author":"Kondaveeti","year":"2013","journal-title":"J. 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