RESUMO
Alzheimer's disease (AD) is a common neurodegenerative disease having complex pathogenesis, approved drugs can only alleviate symptoms of AD for a period of time. Traditional Chinese medicine (TCM) contains multiple active ingredients that can act on multiple targets simultaneously. In this paper, a novel algorithm based on entropy and random walk with the restart of heterogeneous network (RWRHE) is proposed for predicting active ingredients for AD and screening out the effective TCMs for AD. First, Six TCM compounds containing 20 herbs from the AD drug reviews in the CNKI (China National Knowledge Internet) are collected, their active ingredients and targets are retrieved from different databases. Then, comprehensive similarity networks of active ingredients and targets are constructed based on different aspects and entropy weight, respectively. A comprehensive heterogeneous network is constructed by integrating the known active ingredient-target association information and two comprehensive similarity networks. Subsequently, bi-random walks are applied on the heterogeneous network to predict active ingredient-target associations. AD related targets are selected as the seed nodes, a random walk is carried out on the target similarity network to predict the AD-target associations, and the associations of AD-active ingredients are inferred and scored. The effective herbs and compounds for AD are screened out based on their active ingredients' scores. The results measured by machine learning and bioinformatics show that the RWRHE algorithm achieves better prediction accuracy, the top 15 active ingredients may act as multi-target agents in the prevention and treatment of AD, Danshen, Gouteng and Chaihu are recommended as effective TCMs for AD, Yiqitongyutang is recommended as effective compound for AD.
Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doenças Neurodegenerativas , Humanos , Medicina Tradicional Chinesa , Doença de Alzheimer/tratamento farmacológico , Entropia , Farmacologia em Rede , Doenças Neurodegenerativas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Simulação de Acoplamento MolecularRESUMO
Polysaccharide extracted from the Maitake mushroom (MP) is considered as a potential anticancer agent. The present study was performed to investigate the cytotoxic effects of MP and vitamin C (VC) alone and in combination on the viability of human neuroglioma M059 K cells in vitro. A combination of MP (1.0 mg/mL) and VC (0.4 mmol/L) led to a 53.10% reduction in cell viability and this treatment induced cell cycle arrest at the G2/M phase, and apoptosis occurred in 38.54% of the cells. Results of Hoechst 33258 staining and Western blot showed apoptotic cells appeared and changes in the expression of apoptosis-related proteins (upregulation of Bax and caspase-3, downregulation of Bcl-2, and activation of poly-(ADP-ribose)-polymerase). Moreover, the activities of caspase-3, caspase-8, and caspase-9 were enhanced in M059 K cells. The inhibiting effect of combined treatment with MP and VC on M059 K cells indicates the mechanism of anticancer activity involved induction of cell apoptosis.