Andalucin from Artemisia lannta suppresses the neuroinflammation via the promotion of Nrf2-mediated HO-1 levels by blocking the p65-p300 interaction in LPS-activated BV2 microglia
| Autor: | Ya-Nan Gai, Xin Wang, Li-Li Huang, Bing-Bing Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides NF-E2-Related Factor 2 Pharmaceutical Science Pharmacology Sesquiterpene lactone 03 medical and health sciences Lactones Mice Western blot Drug Discovery medicine Animals Luciferase Neuroinflammation chemistry.chemical_classification Messenger RNA medicine.diagnostic_test Chemistry Anti-Inflammatory Agents Non-Steroidal Transcription Factor RelA Membrane Proteins In vitro Crosstalk (biology) 030104 developmental biology Complementary and alternative medicine Artemisia Cyclooxygenase 2 Molecular Medicine Cytokines Microglia Signal transduction human activities E1A-Associated p300 Protein Sesquiterpenes Heme Oxygenase-1 Signal Transduction |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 51 |
| ISSN: | 1618-095X |
| Popis: | Background Neuroinflammation plays an important role in many neurodegenerative conditions such as Alzheimer's disease (AD) and Parkinson disease (PD). Andalucin (ADL), a sesquiterpene lactone from Artemisia lannta, has been reported to exhibit NO inhibition in vitro. However, the effect of ADL on microglia-mediated neuroinflammation has not been investigated. Purpose This study was designed to determine the anti-neuroinflammatory effect of ADL against LPS-activated BV2 microglial cells and to explore the underlying mechanisms. Methods The production of pro-inflammatory mediators and cytokines were measured by ELISA. The relevant mechanisms were analyzed by qRT-PCR, Luciferase assay, Western blot and Co-immunoprecipitation Assay. Results ADL inhibited the LPS-induced release of NO, PGE2, TNF-α, IL-6 and IL-1β. In addition, ADL reduced the mRNA and protein levels of iNOS and COX-2. Mechanism studies found that ADL activated Nrf2/HO-1 signaling pathway and suppressed NF-κB signaling pathway. Further investigation showed that the stimulative effect of ADL on Nrf2 transcriptional activity and the inhibitory effect of ADL on RelA transcriptional activity were due to its regulation on p300-Nrf2/p65 interaction. Conclusion ADL displayed anti-neuroinflammatory activity in LPS-activated BV2 cells. The mechanism concerns its regulatory effect on the crosstalk between Nrf2 and p65. |
| Databáze: | OpenAIRE |
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