Silver nano particles ameliorate learning and spatial memory of male Wistar rats by prevention of amyloid fibril-induced neurotoxicity.

Alzheimer's disease (AD) is a chronic degenerative disease characterized by the presence of amyloid plaques and neurofibrillary tangles (NFTs), which results into memory and learning impairments. In the present study, we showed that the aggregates formed by a protein that has no link with Alzheimer's disease, namely the hen egg white lysozyme (HEWL), were cytotoxic and decreased spatial learning and memory in rats. The effect of Ag-nano particles (Ag-NPs) was investigated on disruption of amyloid aggregation and preservation of cognitive behavior of rats. Twenty-four male Wistar rats were divided into 4 groups including a control group, and injected with either scopolamine, lysozyme or aggregates pre-incubated with Ag-NPs. Rats' behavior was monitored using Morris water maze (MWM) twenty days after injections. HEWL aggregation in the presence and absence of the Ag-NPs was assayed by Thioflavin T binding, atomic force microscopy and cell-based cytotoxicity assay. Ag-NPs were capable to directly disrupt HEWL oligomerization and the resulting aggregates were non-toxic. We also showed that rats of the Ag-NPs group found MWM test platform in less time and with less distance traveled, in comparison with lysozyme group. Ag-NPs also increased the percentage of time elapsed and the distance swum in the target quadrant in the rat model of AD, in probe test. These observations suggest that Ag-NPs improved spatial learning and memory by inhibiting amyloid fibril-induced neurotoxicity. Furthermore, we suggest using model proteins as a valid tool to investigate the pathogenesis of Alzheimer's disease.

In Silico and In Vitro Evaluation of Cytotoxic Activities of Farnesiferol C and Microlobin on MCF-7, HeLa and KYSE Cell Lines.

Background: Cancer is one of the leading causes of death worldwide. Despite certain advances in cancer therapy, still there is considerable demand for developing efficient therapeutic agents. Nowadays, there is a rising interest in the use of natural-based anti-cancer drugs. In this study, the cytotoxicity of farnesiferol C and microlobin isolated from Ferula szowitsiana was investigated against MCF-7, HeLa and KYSE cancer cell lines. In addition, the mechanism of binding of these compounds to apoptotic proteins (Bax, Bak and Bcl-2) was analyzed by an in silico method. Materials and methods: We used MTT assay in order to assess the cytotoxicity of compounds against cancer cell lines. For in silico study, the AutoDock 4 was adopted. Results and discussion: According to the in vitro findings, in general, farnesiferol C showed significant cytotoxicity at higher concentrations (>50 µM) following 48 and 72 h incubation with the selected cancer cells; however, microlobin exhibited almost no activity at concentrations up to 100 µM. The in silico results revealed that both compounds could bind to Bax more efficiently rather than to Bcl-2 or Bak proteins. Conclusion: The results obtained by our preliminary in vitro and in silico studies suggest that these compounds might induce apoptosis through Bax activation; however further studies, either in vitro or in vivo are needed to clarify these activities.