Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway
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 inflam...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.714554/full |
| _version_ | 1819174466583789568 |
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| author | Honglin Xu Min Liu Guanghong Chen Yuting Wu Yuting Wu Lingpeng Xie Xin Han Guoyong Zhang Zhangbin Tan Wenjun Ding Huijie Fan Hongmei Chen Bin Liu Yingchun Zhou |
| author_facet | Honglin Xu Min Liu Guanghong Chen Yuting Wu Yuting Wu Lingpeng Xie Xin Han Guoyong Zhang Zhangbin Tan Wenjun Ding Huijie Fan Hongmei Chen Bin Liu Yingchun Zhou |
| author_sort | Honglin Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T20:39:25Z |
| format | Article |
| id | doaj.art-db6d56c99f18426ca69b2bfb4819508a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T20:39:25Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-db6d56c99f18426ca69b2bfb4819508a2022-12-21T18:13:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.714554714554Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling PathwayHonglin Xu0Min Liu1Guanghong Chen2Yuting Wu3Yuting Wu4Lingpeng Xie5Xin Han6Guoyong Zhang7Zhangbin Tan8Wenjun Ding9Huijie Fan10Hongmei Chen11Bin Liu12Yingchun Zhou13Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, Binzhou Medical University Hospital, Binzhou, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment 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, ChinaDepartment 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, ChinaTCM Health Construction Department of Yangjiang People’s Hospital, Yangjiang, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaDepartment 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, ChinaDepartment of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaPanax 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.714554/fullanti-inflammatory effectsginsenoside Rb3MAPKNF-κBTLR4 |
| spellingShingle | Honglin Xu Min Liu Guanghong Chen Yuting Wu Yuting Wu Lingpeng Xie Xin Han Guoyong Zhang Zhangbin Tan Wenjun Ding Huijie Fan Hongmei Chen Bin Liu Yingchun Zhou Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway Frontiers in Pharmacology anti-inflammatory effects ginsenoside Rb3 MAPK NF-κB TLR4 |
| title | Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway |
| title_full | Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway |
| title_fullStr | Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway |
| title_full_unstemmed | Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway |
| title_short | Anti-Inflammatory Effects of Ginsenoside Rb3 in LPS-Induced Macrophages Through Direct Inhibition of TLR4 Signaling Pathway |
| title_sort | anti inflammatory effects of ginsenoside rb3 in lps induced macrophages through direct inhibition of tlr4 signaling pathway |
| topic | anti-inflammatory effects ginsenoside Rb3 MAPK NF-κB TLR4 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.714554/full |
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