RESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Autofagia , Caenorhabditis elegans , Dendrobium , Modelos Animais de Doenças , Extratos Vegetais , Proteostase , Animais , Caenorhabditis elegans/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Dendrobium/química , Proteostase/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Extratos Vegetais/farmacologia , Animais Geneticamente Modificados , Proteínas tau/metabolismo , Fenóis/farmacologia , Fenóis/isolamento & purificação , Flavanonas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Coix seed oil (CSO) has many beneficial effects, but there is limited research on its influence on the processes and mechanisms related to senescence. Here, we used Caenorhabditis elegans as an in vivo model to investigate CSO's bioeffects on longevity. CSO (1 mg/mL) significantly extended the mean lifespan of C. elegans by over 22.79% and markedly improved stress resistance. Gene-specific mutant studies showed that the CSO-mediated increase in life expectancy was dependent on mev-1, hsf-1 and daf-16, but not daf-2. Furthermore, CSO significantly upregulated stress-inducible genes, including daf-16 and its downstream genes (sod-3, hsp-16.2 and gst-4). In addition, four major fatty acids, linoleic, oleic, palmitic and stearic, played leading roles in C. elegans' extended lifespan. Thus, CSO increased the life expectancy of, and enhanced the stress resistance in, C. elegans mainly through daf-16 and its downstream genes, but not through the insulin/insulin-like growth factor 1 signaling pathway.