Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-κB and MAPK signaling in in vitro and in vivo models
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 mu M). The results indicated that pretreatment with lirioresinol B dimethyl ether significantly suppressed nuclear factor kappa B (NF-kappa B) 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-kappa B 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 I kappa B alpha. Lirioresinol B dimethyl ether also significantly down-regulated the phosphorylation of Jun N-terminal kinase (JNK), p-38 and extracellular signal-regulated kinase (ERR). 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-kappa B activation.
第一作者单位：[1]Huazhong Univ Sci & Technol,Tongji Med Coll,Dept Cardiothoras & Vasc Surg,Tongji Hosp,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Su Yunshu,Xiong Sizheng,Lan Hongwen,et al.Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-κB and MAPK signaling in in vitro and in vivo models[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2019,73:321-332.doi:10.1016/j.intimp.2019.05.020.
APA：
Su, Yunshu,Xiong, Sizheng,Lan, Hongwen,Xu, Lijun&Wei, Xiang.(2019).Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-κB and MAPK signaling in in vitro and in vivo models.INTERNATIONAL IMMUNOPHARMACOLOGY,73,
MLA：
Su, Yunshu,et al."Molecular mechanism underlying anti-inflammatory activities of lirioresinol B dimethyl ether through suppression of NF-κB and MAPK signaling in in vitro and in vivo models".INTERNATIONAL IMMUNOPHARMACOLOGY 73.(2019):321-332
