RESUMO
BACKGROUND: Systemic inflammation is known as a risk factor of cognitive decline. OBJECTIVE: To investigate the effects of propolis on cognitive decline and systemic inflammation in elderly people living at high altitude. METHODS: Sixty participants (average 72.8 years) living at altitude (2,260 meters) were randomized to receive propolis (0.83âg, nâ=â30) or placebo (nâ=â30) for 24 months. Cognitive outcomes were assessed using MMSE and serum cytokine levels were measured for 24 months in a double-blind study. RESULTS: MMSE scores were 26.17 at baseline and 23.87 at 24 months in placebo group. Compared to placebo group, improvements of MMSE scores were significant in propolis-treated subjects (pâ=â0.007) with a response emerging over time (time points×group interaction, pâ=â0.016). In addition, the serum IL-1ß and IL-6 levels were significantly different across treatments (pâ<â0.0001) showing upward and downward trends in placebo- and propolis-treated subjects, respectively (pâ<â0.0001). Serum levels of TNF-α were not significantly different across treatment (pâ=â0.0528) but with a response emerging over time (time points×group interaction, pâ=â0.016). In contrast, serum levels of TGFß1 were significantly different across treatments (pâ<â0.0001) showing downward and upward trends in placebo- and propolis-treated subjects, respectively. Serum levels of IL-10 were significant for the effect of groups (pâ=â0.0411). Furthermore, MMSE scores correlated with the decrease in IL-1ß and the increase in TGFß1 in serum. CONCLUSION: Elderly people living at high altitude developed to MCI in 24 months with exacerbation of systemic inflammation. Ingestion of propolis (>12 months) protected against cognitive decline after systemic inflammation was reduced.
Assuntos
Altitude , Anti-Inflamatórios não Esteroides/uso terapêutico , Apiterapia , Disfunção Cognitiva/prevenção & controle , Inflamação/tratamento farmacológico , Própole/uso terapêutico , Idoso , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/psicologia , Masculino , Testes de Estado Mental e Demência , Resultado do TratamentoRESUMO
Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer's disease (AD). We have found that Brazilian green propolis (propolis) improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF), and activity-regulated cytoskeleton-associated protein (Arc), the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS) derived from mitochondria and 8-oxo-2'-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker) but significantly reversed the fibrillar ß-amyloid and IL-1ß-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K). These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging.