Back to Search Start Over

Ginsenoside Rh 2 Alleviates LPS-Induced Inflammatory Responses by Binding to TLR 4 /MD-2 and Blocking TLR 4 Dimerization.

Authors :
Pan, Shujuan
Peng, Luyuan
Yi, Qion
Qi, Weijin
Yang, Hui
Wang, Hongying
Wang, Lu
Source :
International Journal of Molecular Sciences. Sep2024, Vol. 25 Issue 17, p9546. 12p.
Publication Year :
2024

Abstract

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-α (TNF-α) 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-κB 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
25
Issue :
17
Database :
Academic Search Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
179644623
Full Text :
https://doi.org/10.3390/ijms25179546