Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway
| العنوان: | Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway |
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| المؤلفون: | Gui-qiong Huang, Zhang-Bin Tan, Hong-Mei Chen, Hui-Jie Fan, Ling-Peng Xie, Bin Liu, Yu-Ting Wu, Guanghong Chen, Ying-Chun Zhou, Min Liu, Hong-Lin Xu |
| المصدر: | Journal of Ginseng Research, Vol 46, Iss 1, Pp 156-166 (2022) Journal of Ginseng Research |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | 0301 basic medicine, Ginsenoside Ro, Lipopolysaccharide, Lung injury, Biochemistry, Genetics and Molecular Biology (miscellaneous), NF-κB, 03 medical and health sciences, chemistry.chemical_compound, Ginseng, 0302 clinical medicine, MAPKs, Inflammation, Toll-like receptor, Chemistry, Kinase, Botany, Toll like receptor 4, Cell biology, 030104 developmental biology, Complementary and alternative medicine, 030220 oncology & carcinogenesis, QK1-989, TLR4, Phosphorylation, lipids (amino acids, peptides, and proteins), Signal transduction, Research Article, Biotechnology |
| الوصف: | Background Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10−9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway. Graphical abstract Image 1 |
| اللغة: | English |
| تدمد: | 1226-8453 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7533eec779716bf986129fa46a461bfc http://www.sciencedirect.com/science/article/pii/S1226845321000816 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7533eec779716bf986129fa46a461bfc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 12268453 |
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