RESUMO
Recent evidence indicates that microglial activation and hippocampal damage may play important roles in neurodegenerative diseases, including Alzheimer's disease. Bambusae Caulis in Taeniam has been used as a folk remedy for the treatment of hypertension and cardiovascular disease in China and Korea. In this study, the mechanism responsible for the neuroprotective and anti-neuroinflammatory effects of Bambusae Caulis in Taeniam ethyl acetate fraction (BCE) was investigated. Heme oxygenase-1 (HO-1) is an inducible enzyme expressed in response to various inflammatory stimuli. Due to its role in the anti-inflammatory signaling pathway, the expression and modulation of HO-1 are important. In this study, the neuroprotective and anti-neuroinflammatory effects of BCE were examined using the murine microglial BV2 and hippocampal HT22 cells. We demonstrated that the administration of BCE provided neuroprotective effects against glutamate-induced cytotoxicity in HT22 cells through the HO-1 and nuclear erythroid-2 related factor 2 (Nrf-2) signaling pathways. We also reported that BCE inhibited lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and that the presence of selective inhibitors of HO-1 (SnPP) resulted in the inhibition of BCE-mediated anti-inflammatory activity in BV2 microglial cells. BCE was shown to induce HO-1 expression as well as the nuclear translocation of Nrf-2 in both microglial and hippocampal cells. These findings revealed the potential therapeutic mechanisms of BCE in neurodegenerative diseases, suggesting that HO-1 and Nrf-2 signaling may play important roles in the mediation of its neuroprotective and anti-neuroinflammatory effects.
Assuntos
Anti-Inflamatórios/farmacologia , Bambusa/química , Medicamentos de Ervas Chinesas/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Citocinas/farmacologia , Citocinas/fisiologia , Indução Enzimática/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Ácido Glutâmico/fisiologia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Hipocampo/citologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Microglia/imunologia , Microglia/fisiologia , Fator 2 Relacionado a NF-E2/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/imunologia , Neurônios/fisiologia , Nitritos/metabolismo , Transporte Proteico , Espécies Reativas de Oxigênio/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
Periodontitis is an oral chronic inflammatory disease that influences systemic diseases. Heme oxygenase-1 has several beneficial abilities through Nrf-2 regulation. Ginkgo biloba has been reported to have anti-inflammatory effects associated with heme oxygenase-1 (HO-1) expression. In this study, we investigated whether the anti-inflammatory effects of G. biloba were involved with Nrf-2-mediated HO-1 expression in Porphyromonas gingivalis LPS-stimulated RAW264.7 macrophage cells. G. biloba was extracted with ethyl acetate (EGB). EGB exhibited anti-inflammatory activities, which suppressed the production of pro-inflammatory mediators, the activation of mitogen-activated protein kinases, and nuclear translocation of transcription factors. EGB also up-regulated the HO-1 expression, and the Nrf-2 level in the nucleus and its transactivity. Furthermore, reduced pro-inflammatory mediator levels by EGB were inverted in the presence of SnPP. The collective results suggest that the anti-inflammatory effects of EGB are due to the HO-1 expression via up-regulation of Nrf-2 in RAW 264.7 cells stimulated by P. gingivalis LPS.