title: Total alkaloids from Radix Linderae prevent the production of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by suppressing NF-kappaB and MAPKs activation.
abstract: Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm (L. strychnifolia Vill), has been long-term used in traditional Chinese medicine for treating various diseases, and alkaloids are believed to be the main active components. Previously, we reported that the total alkaloids from Radix Linderae (TARL) could effectively alleviate inflammation and protect joints from destruction in mouse collagen-induced arthritis, an animal model of human rheumatoid arthritis (RA). To get insight into the underlying mechanisms of TARL, the present study was performed to investigate the effects of TARL on the activation of macrophages and resultant production of inflammatory mediators. In vitro, TARL concentration-dependently prevented the production of nitric oxide, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as the expressions of iNOS, IL-1beta and TNF-alpha mRNA in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). However, it showed little effect on the production of interleukin-6 (IL-6) and the expression of IL-6 mRNA. Signal transduction studies showed that TARL significantly down-regulated the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase rather than c-jun NH(2)-terminal kinase (JNK). Additionally, TARL prominently decreased LPS-induced activation of IKKalpha and phosphorylation of p65 on serine 276, but had little impact on the phosphorylation and degradation of IkappaBalpha. In summary, our results demonstrate that TARL exhibits inhibitory effects on the production of inflammatory mediators from macrophages via blocking NF-kappaB and MAPKs signaling pathways. The findings provide a plausible explanation for the therapeutic efficiency of TARL on the inflammation and joint destruction in RA.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Luo
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Yao
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.forename: Guixin
authors.initials: G
authors.lastname: Chou
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D029626:Ranunculaceae / Q000378:metabolism
chemical_list: D000470:Alkaloids; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts