Ginsenoside Rb1 exerts anti-inflammatory effects in vitro and in vivo by modulating toll-like receptor 4 dimerization and NF-kB/MAPKs signaling pathways |
| |
| Institution: | 1. College of Pharmaceutical Science, Soochow University, Suzhou 215123, China;2. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China;1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China;2. Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China;1. Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China;2. Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing 210042, China;3. Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China;1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, No. 32 Qingquan Road, Yantai 264005, Shandong, China;2. School of Chemistry and Chemical Engineering, Yantai University, No. 32 Qingquan Road, Yantai 264005, Shandong, China;1. Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu province 215123, China;2. Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China;3. College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China;1. Department of Pharmacology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun 130117, China;2. Department of Pathology, The First Hospital of Jilin University, Changchun 130000, China |
| |
| Abstract: | BackgoundGinsenoside Rb1, the main active constituent of Panax ginseng, displays significant anti-inflammatory activity, although the mechanism has not been clearly unraveled. In this study, Rb1’s mechanism of anti-inflammatory effects were investigated.MethodsThe flow cytometry and enzyme-linked immunosorbent assay (ELISA) were empolyed to detect pro-inflammatory cytokines release. The related protein and gene expression was investigated by western blotting and qRT-PCR. The dimerization of TLR4 was measured by co-immunoprecipitation and molecular docking assays. Cellular thermal shift assay was used for the determination of the binding of Rb1 and TLR4. For animal moldels, LPS- or cantharidin-induced acute kidney injury, LPS-induced septic death, and dimethyl benzene-induced ear edema were employed to investigate Rb1’s anti-inflammatory activity in vivo.ResultsRb1 significantly decreased inflammatory cytokines release in LPS-stimulated RAW264.7 cells and BMDMs, as well as COX-2 and iNOS amounts. Rb1 reduced LPS-associated calcium influx, ROS production, and NO generation. The NF-κB and MAPK axes participated in Rb1’s anti-inflammatory effects. Molecular docking simulation indicated Rb1 bound to TLR4 to prevent TLR4 dimerization, as confirmed by co-immunoprecipitation and cellular thermal shift assay. Furthermore, MyD88 recruitment and TAK1 expression were altered by reduced TLR4 dimerization, indicating the TLR4-MyD88-NF-κB/MAPK pathways contributed to Rb1’s anti-inflammatory process. In animal models, Rb1 markedly alleviated LPS- or cantharidin-induced acute kidney injury, rescued LPS-induced septic mice from death, and inhibited dimethyl benzene-induced mouse ear edema.ConclusionOverall, these findings demonstrate Rb1 exhibits marked anti-inflammatory effects, suggesting Rb1 represents an optimal molecule for treating inflammatory diseases. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
