PMID- 31129419 OWN - NLM STAT- MEDLINE DCOM- 20200128 LR - 20231213 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 73 DP - 2019 Aug TI - Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-kappaB and MAPK signaling in in vitro and in vivo models. PG - 321-332 LID - S1567-5769(19)30639-3 [pii] LID - 10.1016/j.intimp.2019.05.020 [doi] AB - The aim of the present study is to explore the anti-inflammatory mechanism of lirioresinol B dimethyl ether via inhibition of multiple signaling pathways in both in vitro and in vivo pharmacological models. To determine the anti-inflammatory activity of the lirioresinol B dimethyl ether, RAW 264.7 macrophages challenged with lipopolysaccharide (LPS) were treated with various concentrations of lirioresinol B dimethyl ether (5, 15, 25, and 50 muM). The results indicated that pretreatment with lirioresinol B dimethyl ether significantly suppressed nuclear factor kappa B (NF-kappaB) activation, nitric oxide (NO) production, the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Lirioresinol B dimethyl ether inhibited LPS-induced activation of production of pro-inflammatory cytokines as well as prostaglandin E(2) (PGE(2)) release. The results obtained by electrophoretic mobility shift assay (EMSA) demonstrated a concentration dependent reduction of the LPS-stimulated activation of NF-kappaB and activator protein-1 (AP-1) by lirioresinol B dimethyl ether in in vitro and in vivo models. Moreover, lirioresinol B dimethyl ether also reduced the expression of toll-like receptor (TLR)-4 protein and myeloid differentiation primary response gene 88 (MyD88) as well as promoted the degradation of IkappaBalpha. Lirioresinol B dimethyl ether also significantly down-regulated the phosphorylation of Jun N-terminal kinase (JNK), p-38 and extracellular signal-regulated kinase (ERK). Furthermore, the results of acute and chronic inflammation demonstrated that lirioresinol B dimethyl ether (10 and 50 mg per kg) reduced paw edema and mechanical hyperalgesia in carrageenan- and Complete Freund's Adjuvant (CFA)-induced in vivo mouse models, respectively. Hence, the current results indicate that lirioresinol B dimethyl ether either act by inhibiting pro-inflammatory mediators through down-regulation of mitogen activated protein kinases (MAPKs) signaling pathways and reduction of NF-kappaB activation. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Su, Yunshu AU - Su Y AD - Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: micxu@163.com. FAU - Xiong, Sizheng AU - Xiong S AD - Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. FAU - Lan, Hongwen AU - Lan H AD - Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. FAU - Xu, Lijun AU - Xu L AD - Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: n803ve@163.com. FAU - Wei, Xiang AU - Wei X AD - Department of Cardiothorasic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: xiangwei201808@163.com. LA - eng PT - Journal Article DEP - 20190523 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Furans) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (lirioresinol B dimethyl ether) RN - 31C4KY9ESH (Nitric Oxide) RN - 9000-07-1 (Carrageenan) RN - 9007-81-2 (Freund's Adjuvant) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology/therapeutic use MH - Carrageenan MH - Cell Survival/drug effects MH - Cytokines/metabolism MH - Dinoprostone/metabolism MH - Edema/chemically induced/drug therapy MH - Freund's Adjuvant MH - Furans/*pharmacology/therapeutic use MH - Hyperalgesia/chemically induced/drug therapy MH - Lipopolysaccharides/pharmacology MH - Male MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - NF-kappa B/*metabolism MH - Nitric Oxide/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - RAW 264.7 Cells MH - Signal Transduction/drug effects MH - NF-kappaB-Inducing Kinase OTO - NOTNLM OT - Anti-inflammatory OT - Carrageenan OT - Lirioresinol B dimethyl ether OT - MAPKs/AP-1 OT - NF-kappaB EDAT- 2019/05/28 06:00 MHDA- 2020/01/29 06:00 CRDT- 2019/05/27 06:00 PHST- 2019/03/26 00:00 [received] PHST- 2019/04/15 00:00 [revised] PHST- 2019/05/10 00:00 [accepted] PHST- 2019/05/28 06:00 [pubmed] PHST- 2020/01/29 06:00 [medline] PHST- 2019/05/27 06:00 [entrez] AID - S1567-5769(19)30639-3 [pii] AID - 10.1016/j.intimp.2019.05.020 [doi] PST - ppublish SO - Int Immunopharmacol. 2019 Aug;73:321-332. doi: 10.1016/j.intimp.2019.05.020. Epub 2019 May 23.