title: Anti-inflammatory potential of Rikkosan based on IL-1β network through macrophages to oral tissue cells.
abstract: 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 E2 (PGE2) production, but inhibited interleukin-1β (IL-1β) (5 ng/ml)-stimulated PGE2 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-α (TNF-α) 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-α production, however, declined significantly regardless of the presence or absence of LPS. Rikkosan dose-dependently inhibited IL-1β 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-α and IL-1β productions in activated RAW264.7 cells, but to lower extents than that of Rikkosan. These results demonstrated that Rikkosan inhibited both IL-1β production by LPS-activated macrophages and PGE2 production by IL-1β-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-1β network through macrophages to oral tissue cells.
authors: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan Department of Oral Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan sakagami@dent.meikai.ac.jp horien@saitama-med.ac.jp.
authors: Norio
authors: N
authors: Horie
authors: Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors: Ken
authors: K
authors: Hashimoto
authors: Department of Oral Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors: Shunsuke
authors: S
authors: Hino
authors: Department of Oral Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors: Takao
authors: T
authors: Kato
authors: Department of Oral Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors: Tetsuo
authors: T
authors: Shimoyama
authors: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors: Tadayoshi
authors: T
authors: Kaneko
authors: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors: Kaoru
authors: K
authors: Kusama
authors: Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan sakagami@dent.meikai.ac.jp horien@saitama-med.ac.jp.
authors: Hiroshi
authors: H
authors: Sakagami
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone
keywords: Rikkosan; human gingival fibroblast; interleukin-1β; mouse macrophage-like RAW264.7 cells; periodontal ligament fibroblast; prostaglandin E2