{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T20:36:12Z","timestamp":1782506172445,"version":"3.54.5"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Alzheimer\u2019s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer\u2019s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that A\u00df oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When A\u00df binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer\u2019s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Result<\/jats:title>\n<jats:p>In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal\/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex\u2019s dynamic development.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0279616","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T18:30:38Z","timestamp":1674153038000},"page":"e0279616","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-6633","authenticated-orcid":true,"given":"Sandip","family":"Debnath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devesh","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somdatta Yashwant","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Afzal","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul Subhash","family":"Buchade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3622-9555","authenticated-orcid":true,"given":"Kavindra Kumar","family":"Kesari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2362-185X","authenticated-orcid":true,"given":"Abdel-Fattah M.","family":"Abdel-Fattah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-8934","authenticated-orcid":true,"given":"Mohammad","family":"Algahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayyadah","family":"Mheidat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawidh","family":"Alsaidalani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany A.","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-2713","authenticated-orcid":true,"given":"Mohamed M.","family":"Abdel-Daim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"issue":"4","key":"pone.0279616.ref001","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"GS Bloom","year":"2014","journal-title":"JAMA Neurol"},{"issue":"1","key":"pone.0279616.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/alzrt24","article-title":"Inflammation in Alzheimer\u2019s disease: relevance to pathogenesis and therapy","volume":"2","author":"E Zotova","year":"2010","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"pone.0279616.ref003","doi-asserted-by":"crossref","first-page":"a006346","DOI":"10.1101\/cshperspect.a006346","article-title":"Inflammation in Alzheimer disease\u2014a brief review of the basic science and clinical literature","volume":"2","author":"T Wyss-Coray","year":"2012","journal-title":"Cold Spring Harbor perspectives in medicine"},{"key":"pone.0279616.ref004","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.neurobiolaging.2014.09.027","article-title":"Alzheimer\u2019s disease is associated with altered expression of genes involved in immune response and mitochondrial processes in astrocytes","volume":"36","author":"S. 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