Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway

Frontiers in Pharmacology

Zhangbin Tan¹  Wenjun Ding¹  Bin Liu¹  Yuting Wu²  Hongmei Chen³  Yingchun Zhou³  Guanghong Chen³  Guoyong Zhang³  Honglin Xu³  Lingpeng Xie³  Xin Han³  Min Liu⁴  Huijie Fan⁵ 

[1]Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

[2]Department of Traditional Chinese Medicine, Binzhou Medical University Hospital, Binzhou, China

[3]Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China

[4]Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China

[5]TCM Health Construction Department of Yangjiang People’s Hospital, Yangjiang, China

关键词: anti-inflammatory effects;    ginsenoside Rb3;    MAPK;    NF-κB;    TLR4;   

DOI  :  10.3389/fphar.2022.714554

来源: DOAJ

【 摘 要 】

Panax ginseng has therapeutic effects on various inflammation-related diseases. Ginsenoside Rb3 (GRb3), a natural compound with anti-inflammatory and immunomodulatory properties, is one of the main active panaxadiol extracted from Panax ginseng. We explored whether GRb3 inhibited LPS-mediated inflammation through TLR4/NF-κB/MAPK signaling in macrophages. GRb3 attenuated NO and PGE2 production by attenuating iNOS and COX2 expression. GRb3 also suppressed pro-inflammatory cytokines levels, including IL-1β, IL-6, and TNF-α. Moreover, GRb3 administration significantly suppressed NF-κB (p65) nuclear translocation and the phosphorylation levels of p65, IκBα, JNK, p38, and ERK dose-dependently. Molecular docking demonstrated that GRb3 could dock onto the hydrophobic binding site of TLR4/MD2 complex, with a binding energy of −8.79 kcal/mol. Molecular dynamics (MD) displayed stable TLR4-MD2-GRb3 modeling. GRb3 dose-dependently inhibited LPS binding to cell membranes and blocked TLR4 expression. Surface plasmon resonance imaging (SPRi) revealed that GRb3 had an excellent binding affinity to TLR4/MD2 complex. Notably, resatorvid (TAK242), a selective TLR4 inhibitor, did not increase the repressive influence of GRb3 in RAW264.7 macrophages. Moreover, TLR4 overexpression partially reversed the repressive roles of GRb3 on the NF-κB/MAPK pathway and inflammatory mediators. Collectively, our study strongly indicated that GRb3 attenuated LPS-mediated inflammation through direct inhibition of TLR4 signaling. A novel insight into the underlying mechanism of anti-inflammatory effects of GRb3 in macrophages was confirmed.

【 授权许可】

Unknown