{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:06Z","timestamp":1787028546185,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160849"],"award-info":[{"award-number":["32160849"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273051"],"award-info":[{"award-number":["32273051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31760747"],"award-info":[{"award-number":["31760747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipopolysaccharide (LPS) triggers a severe systemic inflammatory reaction in mammals, with the dimerization of TLR4\/MD-2 upon LPS stimulation serving as the pivotal mechanism in the transmission of inflammatory signals. Ginsenoside Rh2 (G-Rh2), one of the active constituents of red ginseng, exerts potent anti-inflammatory activity. However, whether G-Rh2 can block the TLR4 dimerization to exert anti-inflammatory effects remains unclear. Here, we first investigated the non-cytotoxic concentration of G-Rh2 on RAW 264.7 cells, and detected the releases of pro-inflammatory cytokines in LPS-treated RAW 264.7 cells, and then uncovered the mechanisms involved in the anti-inflammatory activity of G-Rh2 through flow cytometry, fluorescent membrane localization, Western blotting, co-immunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis in LPS-stimulated macrophages. Our results show that G-Rh2 stimulation markedly inhibited the secretion of LPS-induced interleukin-6 (IL-6), tumor necrosis factor-\u03b1 (TNF-\u03b1) and nitric oxide (NO). Additionally, G-Rh2 blocked the binding of LPS with the membrane of RAW 264.7 cells through direct interaction with TLR4 and MD-2 proteins, leading to the disruption of the dimerization of TLR4 and MD-2, followed by suppression of the TLR4\/NF-\u03baB signaling pathway. Our results suggest that G-Rh2 acts as a new inhibitor of TLR4 dimerization and may serve as a promising therapeutic agent against inflammation.<\/jats:p>","DOI":"10.3390\/ijms25179546","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"9546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ginsenoside Rh2 Alleviates LPS-Induced Inflammatory Responses by Binding to TLR4\/MD-2 and Blocking TLR4 Dimerization"],"prefix":"10.3390","volume":"25","author":[{"given":"Shujuan","family":"Pan","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China"},{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyuan","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qion","family":"Yi","sequence":"additional","affiliation":[{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijin","family":"Qi","sequence":"additional","affiliation":[{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China"},{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China"},{"name":"Engineering Research Center of the Utilization for Characteristic Bio-Pharma Ceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114291","DOI":"10.1016\/j.ejmech.2022.114291","article-title":"Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective","volume":"235","author":"Zhang","year":"2022","journal-title":"Eur. 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