Total alkaloids from Radix Linderae prevent the production of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by suppressing NF-κB 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-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as the expressions of iNOS, IL-1β and TNF-α mRNA in RAW 264.7 cells stimulated by lipopolysaccharid (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 NH2-terminal kinase (JNK). Additionally, TARL prominently decreased LPS-induced activation of IKKα and phosphorylation of p65 on serine 276, but had little impact on the phosphorylation and degradation of IκBα. In summary, our results demonstrate that TARL exhibits inhibitory effects on the production of inflammatory mediators from macrophages via blocking NF-κB and MAPKs signaling pathways. The findings provide a plausible explanation for the therapeutic efficiency of TARL on the inflammation and joint destruction in RA. [Copyright &y& Elsevier]