{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:32:51Z","timestamp":1760059971796,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP19678025"],"award-info":[{"award-number":["AP19678025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Organic acids, as natural metabolites, play crucial roles in human metabolism and health. Tumor Necrosis Factor (TNF), a pivotal mediator in immune regulation and inflammation, is a key therapeutic target. We evaluated ten organic acids as TNF modulators using in silico molecular docking, followed by detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling and molecular dynamics (MD) simulations for three lead candidates: gallic, aconitic, and crocetin acids. Their effects on TNF gene expression were then assessed in vivo using a mouse leukocyte model. The in silico results indicated that crocetin had the highest TNF binding affinity (\u22125.6 to \u22124.6 kcal\/mol), while gallic acid formed the most stable protein-ligand complex during MD simulations, and aconitic acid established hydrogen bond interactions. ADMET analysis suggested potential pharmacokinetic limitations, including low permeability. Contrasting its high predicted binding affinity, in vivo gene expression analysis revealed that crocetin stimulated TNF synthesis, whereas gallic and aconitic acids acted as inhibitors. This research explores organic acids as potential TNF modulators, highlighting their complex interactions and providing a foundation for developing these compounds as anti-inflammatory agents targeting TNF-mediated diseases.<\/jats:p>","DOI":"10.3390\/molecules30153175","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T12:39:29Z","timestamp":1753792769000},"page":"3175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gallic, Aconitic, and Crocetin Acids as Potential TNF Modulators: An Integrated Study Combining Molecular Docking, Dynamics Simulations, ADMET Profiling, and Gene Expression Analysis"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-3484","authenticated-orcid":false,"given":"Adolat","family":"Manakbayeva","sequence":"first","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Bogoyavlenskiy","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6691-4969","authenticated-orcid":false,"given":"Timur","family":"Kerimov","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9914-9364","authenticated-orcid":false,"given":"Igor","family":"Yershov","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-3341","authenticated-orcid":false,"given":"Pavel","family":"Alexyuk","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madina","family":"Alexyuk","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-8975","authenticated-orcid":false,"given":"Vladimir","family":"Berezin","sequence":"additional","affiliation":[{"name":"Research and Production Center for Microbiology and Virology, Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5176-7461","authenticated-orcid":false,"given":"Vyacheslav","family":"Dushenkov","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Hostos Community College CUNY, Bronx, NY 10451, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20871","DOI":"10.1021\/acs.est.3c07473","article-title":"Unrecognized Role of Organic Acid in Natural Attenuation of Pollutants by Mackinawite (FeS): The Significance of Carbon-Center Free Radicals","volume":"57","author":"Li","year":"2023","journal-title":"Environ. 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