RESUMO
Alzheimer disease is a complex neurodegenerative disorder. It is the common form of dementia in elderly people. The etiology of this disease is multifactorial, pathologically it is accompanied with accumulation of amyloid beta and neurofibrillary tangles. Accumulation of amyloid beta and mitochondrial dysfunction leads to oxidative stress. In this study, neuroprotective effect of Artemisiaamygdalina against H2O2-induced death was studied in differentiated N2a and SH-SY5Ycells. Cells were treated with H2O2 to induce toxicity which was attenuated by Artemisia amygdalina. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. It controls the basal and induced expression of antioxidant response element-dependent genes. Further, we demonstrated that Artemisia amygdalina protects neurons through upregulation of Nrf2 pathway. Moreover, reactive oxygen species and mitochondrial membrane potential loss formed by H2O2 was attenuated by Artemisia amygdalina. Thus, Artemisia amygdalina may have the possibility to be a therapeutic agent for Alzheimer disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Artemisia/química , Fator 2 Relacionado a NF-E2/genética , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Regulação para Cima , Animais , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Radical Hidroxila/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fenóis/análise , Picratos/química , Extratos Vegetais/farmacologia , Superóxidos/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dipsacus inermis Wall. is an edible Himalayan herb which is extensively used in traditional Ayurvedic system of medicine against various inflammation related disorders. AIM OF THE STUDY: This study was designed to evaluate the anti-inflammatory effects of Dipsacus inermis Wall. methanol extract (DIME) by using in vitro and in vivo models and to elucidate the underlying mechanism of action. MATERIALS AND METHODS: The in vitro anti-inflammatory potential of DIME was determined in LPS stimulated J774A.1â¯cells. The inhibitory effect of DIME on COX-2, PGE2 and inflammatory cytokines was determined by ELISA and RT-PCR. The suppression of ROS in response to DIME was determined by flow cytometry. Phosphorylation of NF-κBp65 and IκB degradation was determined by western blotting. RESULTS: Significant inhibition of NO, COX-2, PGE2 and pro-inflammatory cytokines including IL-1ß, TNF-α and IL-6 was found in response to DIME in LPS stimulated J774A.1â¯cells. The extract was found to down regulate the LPS induced expression of TNF-α, IL-6, iNOS and COX-2 along with inhibition of intracellular ROS. The in vivo studies carried on Wistar rats showed significant preventive effect of DIME against acetic acid induced increase in vascular permeability and carrageenan induced paw edema along with stabilization of histopathological alterations. CONCLUSION: The study demonstrated that DIME has significant in vitro and in vivo anti-inflammatory effect which is mediated by inhibiting the activation of NF-κB pathway. Our data opened a promising new pharmacological approach of designing anti-inflammatory drugs by studying individual fractions of the plant extract.