期刊
PLOS ONE
卷 8, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0066895
关键词
-
资金
- National Science Foundation of China [NSFC 20772009]
- Beijing Municipal Natural Science Foundation [7122097]
The present study aims to investigate the therapeutic effects of LXM-10 by intragastric administration in both acute and chronic inflammatory models, and to explore the underlying molecular mechanisms. The results showed that LXM-10 produced significant anti-inflammatory effects on carrageenan induced paw edema and complete Freund's adjuvant (CFA) induced arthritis, in which LXM-10 inhibited paw swelling in a dose-and time-dependent manner. ELISA analysis showed the production of pro-inflammatory cytokines including TNF-alpha and IL-6 was decreased by LXM-10. Western blot analysis showed that LXM-10 significantly reduced phosphorylation of Janus kinase 2 (JAK2) and further blunted phosphorylation of signal transducer and activator of transcription-3 (STAT3). The effects that LXM-10 had shown were attenuated by methyllycaconitine citrate (an alpha 7 nicotinic acetylcholine receptor antagonist) or tropicamide (an M4 muscarinic acetylcholine receptor antagonist) in vivo. In conclusion, the studies showed that intragastric administration of LXM-10 exerted significant anti-inflammation effects in acute and chronic models, which may be attribute to the activation of alpha 7 nicotinic acetylcholine receptor and M4 muscarinic acetylcholine receptor, thereby inhibiting the JAK2/STAT3 signal pathway, and ultimately reducing the production of pro-inflammatory cytokines of TNF-alpha and IL-6.
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