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学科主题: 药学
题名:
Anti-Inflammation of Spirocyclopiperazinium Salt Compound LXM-10 Targeting alpha 7 nAChR and M4 mAChR and Inhibiting JAK2/STAT3 Pathway in Rats
作者: Zhang, Weiwei1,2; Sun, Qi3; Gao, Xiaoli2; Jiang, Yimin4; Li, Runtao1,3; Ye, Jia1,2
刊名: PLOS ONE
发表日期: 2013-06-28
DOI: 10.1371/journal.pone.0066895
卷: 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
所属项目编号: NSFC 20772009 ; 7122097
项目资助者: National Science Foundation of China ; Beijing Municipal Natural Science Foundation
WOS记录号: WOS:000321148400023
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63893
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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).
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