Anti-neuroinflammatory effects of 20C from Gastrodia elata via regulating autophagy in LPS-activated BV-2 cells through MAPKs and TLR4/Akt/mTOR signaling pathways
| Autor: | Nai-Hong Chen, Ying Chen, Yu-He Yuan, Qian-Hang Shao, Cheng-Gen Zhu, Jiangong Shi, Xiao-ling Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Immunology Anti-Inflammatory Agents Autophagy-Related Proteins Cell Line 03 medical and health sciences Mice Phenols Autophagy Animals Benzhydryl Compounds Phosphorylation Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Inflammation Toll-like receptor Gastrodia Chemistry TOR Serine-Threonine Kinases Cell biology Toll-Like Receptor 4 030104 developmental biology TLR4 Tumor necrosis factor alpha Signal transduction Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Molecular immunology. 99 |
| ISSN: | 1872-9142 |
| Popis: | 20C, a novel bibenzyl compound, is isolated from Gastrodia elata. In our previous study, 20C showed protective effects on tunicamycin-induced endoplasmic reticulum stress, rotenone-induced apoptosis and rotenone-induced oxidative damage. However, the anti-neuroinflammatory effect of 20C is still with limited acquaintance. The objective of this study was to confirm the anti-neuroinflammatory effect of 20C on Lipopolysaccharide (LPS)-activated BV-2 cells and further elucidated the underlying molecular mechanisms. In this study, 20C significantly attenuated the protein levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin (IL)-1β, and secretion of nitric oxide (NO) and tumor necrosis factor (TNF)-α induced by Lipopolysaccharide (LPS) in BV-2 cells. Moreover, 20C up-regulated the levels of autophagy-related proteins in LPS-activated BV-2 cells. The requirement of mitogen-activated protein kinases (MAPKs) has been well documented for regulating the process of autophagy. Both 20C and rapamycin enhanced autophagy by suppressing the phosphorylation of MAPKs signaling pathway. Furthermore, 20C treatment significantly inhibited the levels of toll like receptor 4 (TLR4), phosphorylated-protein kinase B (Akt) and phosphorylated-mechanistic target of rapamycin (mTOR), indicating blocking TLR4/Akt/mTOR might be an underlying basis for the anti-inflammatory effect of 20C. These findings suggest that 20C has therapeutic potential for treating neurodegenerative diseases in the future. |
| Databáze: | OpenAIRE |
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