Sesquiterpene dimer (DSF-52) from Artemisia argyi inhibits microglia-mediated neuroinflammation via suppression of NF-κB,JNK/p38 MAPKs and Jak2/Stat3 signaling pathways |
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Institution: | 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China;2. Department of Medicinal Chemistry and Pharmaceutical Analysis, Logistics College of Chinese People''s Armed Police Forces, Tianjin 300162, China;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;2. Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing 100034, China;3. Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Kangneung 210-340, Republic of Korea |
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Abstract: | Microglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Therefore, novel therapeutics suppressing microglia over-activation could prove useful for neuroprotection in inflammation-mediated neurodegenerative diseases. DSF-52 is a novel sesquiterpene dimer compound isolated from medical plant Artemisia argyi by our group. In this study, we investigated whether DSF-52 inhibited the neuroinflammatory responses in lipopolysaccharide (LPS)-activated microglia. Our findings showed that DSF-52 inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), as well as mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein-1α (MIP-1α) in LPS-activated BV-2 microglia. Moreover, DSF-52 markedly up-regulated mRNA levels of anti-inflammatory cytokine IL-10. Mechanism study indicated that DSF-52 suppressed Akt/IκB/NF-κB inflammation pathway against LPS treatment. Also, DSF-52 down-regulated the phosphorylation levels of JNK and p38 MAPKs, but not ERK. Furthermore, DSF-52 blocked Jak2/Stat3 dependent inflammation pathway through inhibiting Jak2 and Stat3 phosphorylation, as well as Stat3 nuclear translocation. We concluded that the inhibitory ability of DSF-52 on microglia-mediated neuroinflammation may offer a novel neuroprotective modality and could be potentially useful in inflammation-mediated neurodegenerative diseases. |
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Keywords: | Neuroinflammation Microglia Sesquiterpene dimer Signaling pathway |
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