Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats

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 induc...

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Main Authors:	Zhang, Weiwei, Sun, Qi, Gao, Xiaoli, Jiang, Yimin, Li, Runtao, Ye, Jia
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695990/

id	pubmed-3695990
recordtype	oai_dc
spelling	pubmed-36959902013-07-09 Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats Zhang, Weiwei Sun, Qi Gao, Xiaoli Jiang, Yimin Li, Runtao Ye, Jia Research Article 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-α 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 α7 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 α7 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-α and IL-6. Public Library of Science 2013-06-28 /pmc/articles/PMC3695990/ /pubmed/23840548 http://dx.doi.org/10.1371/journal.pone.0066895 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Weiwei Sun, Qi Gao, Xiaoli Jiang, Yimin Li, Runtao Ye, Jia
spellingShingle	Zhang, Weiwei Sun, Qi Gao, Xiaoli Jiang, Yimin Li, Runtao Ye, Jia Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
author_facet	Zhang, Weiwei Sun, Qi Gao, Xiaoli Jiang, Yimin Li, Runtao Ye, Jia
author_sort	Zhang, Weiwei
title	Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
title_short	Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
title_full	Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
title_fullStr	Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
title_full_unstemmed	Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
title_sort	anti-inflammation of spirocyclopiperazinium salt compound lxm-10 targeting α7 nachr and m4 machr and inhibiting jak2/stat3 pathway in rats
description	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-α 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 α7 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 α7 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-α and IL-6.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695990/
_version_	1611990442329505792

Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting α7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats

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