RESUMEN
Ailanthus altissima swingle (ailanthic cortex, AAS) has been used as a traditional medicine for fever, bleeding, infection, and inflammation for many years in Korea. However, its mechanisms have not been examined. In the present study, we investigate the effect of AAS on the mast-cell-mediated allergic and inflammatory reaction using in vivo and in vitro models and elucidate its molecular mechanisms. AAS significantly inhibited compound 48/48-induced edema and systemic anaphylaxis. AAS significantly inhibited passive cutaneous anaphylaxis. AAS inhibited histamine release from rat peritoneal mast cells (RPMCs) in a dose-dependent manner. Moreover, AAS significantly inhibited production of inflammatory cytokines, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. AAS inhibits the IgE or stem cell factor-induced TNF production on RPMCs. In activated HMC-1 cells, the expression level of NF-kappaB/Rel A protein increased in the nucleus, whereas the level of NF-kappaB/Rel A in the nucleus was decreased by AAS treatment. In addition, AAS inhibited the PMACI-induced IkappaBalpha degradation. In conclusion, the present results indicate that AAS has potent anti-anaphylactic and anti-inflammatory properties.
Asunto(s)
Ailanthus/química , Anafilaxia/tratamiento farmacológico , Anafilaxia/inmunología , Citocinas/biosíntesis , Mediadores de Inflamación/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/uso terapéutico , Animales , Edema/patología , Liberación de Histamina/efectos de los fármacos , Humanos , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Fitoterapia , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , p-Metoxi-N-metilfenetilaminaRESUMEN
The most well-known medicinal plant, Panax ginseng (P. ginseng), contains various phytosterols and bioactive triterpene saponins (ginsenosides). Squalene synthase is a key regulatory enzyme for triterpene biosynthesis and overexpression of the squalene synthase confers the hyper-production of triterpene saponins to form transgenic ginseng. In this study, we have investigated whether and how transgenic P. ginseng modulates an inflammatory reaction in a stimulated human mast cell line, HMC-1. It was found that transgenic P. ginseng inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and the expression of cyclooxygenase-2 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMACI)-stimulated HMC-1. Additionally, we have shown that transgenic P. ginseng suppressed the intracellular calcium level induced by PMACI. These results provide new insights into the pharmacological actions of transgenic P. ginseng as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.
Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Interleucina-6/antagonistas & inhibidores , Interleucina-8/antagonistas & inhibidores , Panax , Plantas Modificadas Genéticamente/metabolismo , Calcio/antagonistas & inhibidores , Calcio/metabolismo , Línea Celular , Supervivencia Celular , Ciclooxigenasa 2/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mastocitos/metabolismo , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular diseases. However, little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to investigate the effect of DCWGG on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells compared with unstimulated cells. We showed that DCWGG inhibited the production of TNF-alpha, IL-1alpha, IL-1beta IL-6, and IL-8 induced by LPS in a dose-dependent manner. Also, DCWGG inhibited TNF-alpha, IL-1alpha, IL-beta, IL-6, and IL-8 production-induced DFX in dose-dependent manner. These results suggest that DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.