{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:27:04Z","timestamp":1774880824069,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University, Faculty of Medicine\n\t\t\t\t\t\t\t              https:\/\/ror.org\/05m2fqn25","doi-asserted-by":"publisher","award":["11\/2025"],"award-info":[{"award-number":["11\/2025"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The presence of an unbalanced gut microbiome and the dysregulation of bile acid signalling are considered pivotal causes of various inflammation-based diseases. The Takeda G protein-coupled receptor (TGR5), TGR5 is a bile acid-responsive receptor that modulates inflammatory signalling pathways, making it an enticing molecular target for the discovery of novel anti-inflammatory agents. Herein, a comprehensive in silico approach was employed to identify potential TGR5 agonists from sterol-rich phytocompounds present in Triphala, a traditional polyherbal formulation. Using in silico computational methods, such as molecular docking and molecular dynamics simulations (MDS), we screened the putative agonistic potential of 10 phytocompounds obtained from Terminalia chebula, Terminalia bellirica, and Phyllanthus emblica against the crystal structure of human TGR5 (PDB ID: 7XTQ). Based on binding energy and molecular interactions, ergosterol (\u221212.34 \u00b1 0.17 kcal\/mol) and stigmasterol (\u221210.35 \u00b1 0.04 kcal\/mol) were predicted to be the top and best compounds. Furthermore, the stability of these two compounds in the docked complex was analysed using MDS for 200 ns. The mean C\u03b1 RMSD values were 0.22 \u00b1 0.02 nm for both ergosterol- and stigmasterol-bound complexes, compared to 0.21 \u00b1 0.02 nm for the unbound apo protein. Further, the molecular mechanics\/Poisson\u2013Boltzmann surface area (MMPBSA) analysis revealed that ergosterol exhibited binding free energy (\u2212139.868 \u00b1 12.318 kJ\/mol) comparable to that of the co-crystallised ligand R399 \u221293.424 \u00b1 8.919 kJ\/mol. In silico ADMET predictions indicated acceptable drug-like properties and low toxicity for both compounds. Collectively, these computational findings suggest that ergosterol is a promising putative TGR5 agonist, warranting further experimental validation of its potential role in modulating inflammation-related pathways.<\/jats:p>","DOI":"10.3390\/ijms27073130","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:53Z","timestamp":1774878113000},"page":"3130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Identification of Triphala-Derived Sterol Compounds as Putative Agonists of the Human Takeda G Protein-Coupled Receptor (TGR5)"],"prefix":"10.3390","volume":"27","author":[{"given":"Yathindra Maruthi","family":"Prasad","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sneha Ramaiah","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandita","family":"Shantamurthy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allwin Ebinesar Jacob Samuel","family":"Sehar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirajunnisa Abdul","family":"Razack","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8781","authenticated-orcid":false,"given":"Somdet","family":"Srichairatanakool","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuvaraj","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Acharya Institute of Technology, Bangalore 560107, India"},{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.imj.2022.08.004","article-title":"Correlation between human gut microbiome and diseases","volume":"1","author":"Madhogaria","year":"2022","journal-title":"Infect. 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