Anti-inflammatory Potential of Rikkosan Based on IL-1 beta Network Through Macrophages to Oral Tissue Cells

作者：Horie Norio; Hashimoto Ken; Hino Shunsuke; Kato Takao; Shimoyama Tetsuo; Kaneko Tadayoshi; Kusama Kaoru; Sakagami Hiroshi^*

来源：In Vivo, 2014, 28(4): 563-569.

• Rikkosan
• prostaglandin E-2
• interleukin-1 beta
• human gingival fibroblast
• periodontal ligament fibroblast
• mouse macrophage-like RAW264.7 cells

Rikkosan is a traditional Kampo medicine using the control of oral pain caused by dental caries, pulpitis, periodontitis and stomatitis. In order to provide evidence for its clinical effects, we herein investigated whether Rikkosan inhibits the production of pro-inflammatory substances in human and mouse models of inflammation. Rikkosan alone did not induce prostaglandin E-2 (PGE(2)) production, but inhibited interleukin-1 beta (IL-1 beta) (5 ng/ml)-stimulated PGE(2) production in human gingival fibroblasts and human periodontal ligament fibroblasts, with a selectivity index higher than 4.0 and 4.3, respectively. Rikkosan alone dose-dependently stimulated tumor necrosis factor-alpha (TNF-alpha) production, reaching a peak level slightly lower than that attained by lipopolysaccharide (LPS) at 0.4 mg/ml in mouse macrophage-like RAW264.7 cells. At a higher concentration of Rikkosan (4 mg/ml), TNF-alpha production, however, declined significantly regardless of the presence or absence of LPS. Rikkosan dose-dependently inhibited IL-1 beta production by LPS-stimulated RAW264.7 cells, with a selective index of 7.6. Five constituent extracts of Rikkosan, either alone or in combination, showed similar effects on TNF-alpha and IL-1 beta productions in activated RAW264.7 cells, but to lower extents than that of Rikkosan. These results demonstrated that Rikkosan inhibited both IL-1 beta production by LPS-activated macrophages and PGE(2) production by IL-1 beta-stimulated human gingival fibroblasts and human periodontal ligament fibroblasts, suggesting that anti-inflammatory effects of Rikkosan may partially be generated by the inhibition of these pro-inflammatory substances via the IL-1 beta network through macrophages to oral tissue cells.

• 出版日期2014-8