RESUMO
Bisabolangelone (BISA), isolated from the roots of Angelica koreana, has many pharmacological activities, such as anti-tumor, anti-microbial, antioxidant, and anti-inflammatory activities. In this study, we investigated the anti-inflammatory mechanisms of BISA in dendritic cells (DCs), which play an essential role in innate and adaptive immune responses. BISA attenuated the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-1ß, and tumor necrosis factor-alpha (TNF-α), migration to macrophage inflammatory protein-3 beta, and allo-T cell activating ability of DCs. In addition, BISA affected endocytosis of DCs. Molecular studies showed that BISA suppressed MAPK phosphorylation and nuclear translocation of NF-κB p50/p65. Taken together, our data suggest that BISA inhibited DC functions by blocking MAPK and NF-κB signaling.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Células Dendríticas/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Sesquiterpenos/farmacologia , Angelica/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Células Cultivadas , Citocinas/metabolismo , Citocinese/efeitos dos fármacos , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Endocitose/efeitos dos fármacos , Etnofarmacologia , Feminino , Ativação Linfocitária/efeitos dos fármacos , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Raízes de Plantas/química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , República da Coreia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Polysaccharide (PLP) isolated from Phellinus linteus inhibits tumor growth and metastasis by enhancing immune functions of macrophages, dendritic cells, NK cells, T cells, and B cells. Here, we report that PLP can inhibit the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Although 80% of the NOD mice had developed diabetes by 24 weeks of age, none of the PLP-treated NOD mice developed diabetes. The mean blood glucose levels were 110mg/dl in PLP-treated mice and 499mg/dl in control NOD mice. Histological examination of the pancreatic islets revealed that most of the islets isolated from PLP-treated mice were less infiltrated with lymphocytes compared with those of control mice. Spleen cells from diabetic NOD mice could adaptively transfer diabetes into NOD/SCID mice, but those from PLP-treated NOD mice showed delayed transfer of diabetes. PLP inhibited the expression of inflammatory cytokines, including IFN-gamma, IL-2, and TNF-alpha by Th1 cells and macrophages, but up-regulated IL-4 expression by Th2 cells in NOD mice. PLP did not prevent streptozotocin-induced diabetic development in ICR mice. Taken together, these results suggest that PLP inhibits the development of autoimmune diabetes by regulating cytokine expression.