Abstract |
Recently, microsomal prostaglandin E synthase 1 (mPGES-1) has attracted much attention from pharmacologists as a promising strategy and an attractive target for treating various types of diseases including rheumatoid arthritis (RA), which could preserve the anti-inflammatory effect while reducing the adverse effects often occur during administration of non-steroidal anti-inflammatory drugs ( NSAIDs). Here, we report that sinomenine (SIN) decreased prostaglandin (PG)E2 levels without affecting prostacyclin (PG)I2 and thromboxane (TX)A2 synthesis via selective inhibiting mPGES-1 expression, a possible reason of low risk of cardiovascular event compared with NSAIDs. In addition, mPGES-1 protein expression was down-regulated by SIN treatment in the inflamed paw tissues both in carrageenan-induced edema model in rats and the collagen-II induced arthritis (CIA) model in DBA mice. More interestingly, SIN suppressed the last step of mPGES-1 gene expression by decreasing the DNA binding ability of NF-κB, paving a new way for drug discovery.
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Authors | Hua Zhou, Jian-Xin Liu, Jin-Fang Luo, Chun-Song Cheng, Elaine Lai-Han Leung, Ying Li, Xiao-Hui Su, Zhong-Qiu Liu, Ting-Bo Chen, Fu-Gang Duan, Yan Dong, Yi-Han Zuo, Chong Li, Chon Kit Lio, Ting Li, Pei Luo, Ying Xie, Xiao-Jun Yao, Pei-Xun Wang, Liang Liu |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 142
Pg. 133-144
(10 15 2017)
ISSN: 1873-2968 [Electronic] England |
PMID | 28711625
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Morphinans
- sinomenine
- Prostaglandin-E Synthases
- Ptges protein, mouse
- Ptges protein, rat
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Topics |
- A549 Cells
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects, isolation & purification, pharmacology, therapeutic use)
- Arthritis, Experimental
(drug therapy, immunology)
- Cell Culture Techniques
- Cell Survival
(drug effects)
- Edema
(drug therapy, immunology)
- Female
- Gene Expression
(drug effects)
- Macrophages, Peritoneal
(drug effects)
- Male
- Mice, Inbred DBA
- Morphinans
(adverse effects, isolation & purification, pharmacology, therapeutic use)
- Prostaglandin-E Synthases
(genetics)
- Rats, Sprague-Dawley
- Transfection
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