RESUMO
Recent studies have shown that Nur77 and AMPKα play an important role in regulating adipogenesis and isoalantolactone (ISO) dual-targeting AMPKα and Nur77 inhibits adipogenesis. In this study, we hypothesized that Inula helenium (elecampane) root extract (IHE), which contains two sesquiterpene lactones, alantolactone (ALA) and ISO, as major compounds, might inhibit adipogenesis. Here, we found that ALA and IHE simultaneously target AMPKα and Nur77 and inhibited adipogenic differentiation of 3T3-L1 cells, accompanied by the decreased expression of adipocyte markers. Further mechanistic studies demonstrated that IHE shares similar mechanisms of action with ISO that reduce mitotic clonal expansion during the early phase of adipogenic differentiation and decrease expression of cell cycle regulators. These results suggest that IHE inhibits adipogenesis, in part, through co-regulation of AMPKα and Nur77, and has potential as a therapeutic option for obesity and related metabolic dysfunction.
Assuntos
Inula , Sesquiterpenos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP , Adipogenia , Animais , Diferenciação Celular , Lactonas/farmacologia , Camundongos , Compostos Fitoquímicos , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos de EudesmanoRESUMO
Dendritic cells (DCs) are the most potent antigen-presenting cells (APC) particularly important in the initiation of primary T cell-mediated immune responses. Thus, inhibition of the differentiation and function of DC could lead to the suppression of immunological hyperresponsiveness. Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and has been used as a traditional anti-inflammatory medicine. We investigated suppressive effects of carbohydrate fraction 1 from the water extracts of A. iwayomogi (AIP1) on the differentiation and function of bone marrow-derived dendritic cells. Bone marrow cells were cultured in the presence of granulocyte monocyte-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 6-7 days. Then, non-adherent cells were harvested for subsequent analyses. Percentage(s) of CD11c+ MHC II+ cell population(s) mostly composed of immature or mature DC and the allogeneic T cell stimulating ability of the cells were reduced by AIP1. Proteomic analyses along with RT-PCR revealed that expressions of several proteins including TNF receptor-associated factor (TRAF) 5-like protein, pyruvate kinase M2 (PKM2), and coactosin-like protein 1 (CLP1) were down-regulated upon AIP1 treatment.
Assuntos
Artemisia/química , Carboidratos/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Extratos Vegetais/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Interleucina-4/imunologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Proteoma/metabolismo , Linfócitos T/imunologiaRESUMO
Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction, airway hyperreactivity, and remodeling of the airways. The incidence of asthma is on the rise despite ongoing intensive asthma research. Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found around Korea and has been used as a traditional anti-inflammatory medicine in liver diseases. We investigated suppressive effects of AIP1, a water-soluble carbohydrate fraction from A. iwayomogi on ovalbumin-induced allergic asthma in BALB/c mice and studied the possible mechanisms of its anti-allergic action. AIP1 significantly reduced pulmonary eosinophilia and Th2 cytokine expression in the lungs as well as serum IgE levels. Flow cytometric analysis of lung-infiltrating cells showed that the surface levels of CD11c and MHC II in CD11c+MHC II+ cells, potent dendritic cells, decreased in animals treated with AIP1. Expression of TNF-alpha, one of several proinflammatory cytokines released into the airway during episodes of asthma, was down-regulated by AIP1 injection, suggesting that reduced expression of TNF-alpha could account for the suppression of pulmonary eosinophilia and Th2-type cytokine production by AIP1.