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Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting alpha 7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
Zhang, Weiwei1,2; Sun, Qi3; Gao, Xiaoli2; Jiang, Yimin4; Li, Runtao1,3; Ye, Jia1,2
刊名PLOS ONE
2013-06-28
DOI10.1371/journal.pone.0066895
8期:6
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ANTIINFLAMMATORY PATHWAY ; CYTOKINE PRODUCTION ; SIGNALING PATHWAY ; SEVERE SEPSIS ; VAGUS NERVE ; KAPPA-B ; TRANSCRIPTION ; EXPRESSION ; SURVIVAL ; RELEASE
英文摘要

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.

语种英语
WOS记录号WOS:000321148400023
项目编号NSFC 20772009 ; 7122097
资助机构National Science Foundation of China ; Beijing Municipal Natural Science Foundation
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63893
专题北京大学药学院
北京大学医学部管理机构_医学部
北京大学药学院_化学生物学系
北京大学药学院_分子与细胞药理学系
北京大学医学图书馆_信息咨询部
作者单位1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
2.Peking Univ, Dept Mol & Cellular Pharmacol, Sch Pharmaceut Sci, Beijing 100871, Peoples R China
3.Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100871, Peoples R China
4.Peking Univ, Med & Hlth Anal Ctr, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Weiwei,Sun, Qi,Gao, Xiaoli,et al. Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting alpha 7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats[J]. PLOS ONE,2013,8(6).
APA Zhang, Weiwei,Sun, Qi,Gao, Xiaoli,Jiang, Yimin,Li, Runtao,&Ye, Jia.(2013).Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting alpha 7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats.PLOS ONE,8(6).
MLA Zhang, Weiwei,et al."Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting alpha 7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats".PLOS ONE 8.6(2013).
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