Astaxanthin effectiveness in preventing multiple sclerosis in animal model.

OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG). Splenocytes were assessed to measure the levels of proinflammatory and anti-inflammatory cytokines, proliferation rate and FoxP3+Treg cell frequency. Immunohistochemical examinations were performed on spinal cord and brain tissue. RESULTS: Astaxanthin reduced splenocytes proliferation index and proinflammatory cytokine levels, and vice versa increased the anti-inflammatory cytokine levels. Immunohistochemical studies of the spinal cord and brain showed that the infiltration with inflammatory cells was highly confined in the central nervous system. Protective effects of astaxanthin were visible by assigning low score recording in clinical behavior and disease severity. CONCLUSION: Astaxanthin is a powerful tool for intervention in EAE on a model of multiple sclerosis, so it can be studied further to prevent and treat MS (Tab. 2, Fig. 3, Ref. 41).

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.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids.

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Betanin effect on PPAR-α and SREBP-1c expression in NMRI mice model of steatohepatitis with fibrosis.

PURPOSE: Betanin is a betacyanin with antioxidant and anti-inflammatory activities whose effects were investigated in a nonalcoholic steatohepatitis (NASH) model. MAIN METHODS: Ninety-six male naval medical research institute (NMRI) mice were divided into eight groups (n = 12) including normal control, high fat diet (HFD), Sham, and positive control treated with trans-chalcone. Three experimental groups were treated with 5 mg/kg, 10 mg/kg or 20 mg/kg betanin, and a betanin protective group was also defined. RESULTS: Four weeks of HFD treatment resulted in steatohepatitis with associated fibrosis. Significant increase was observed in serum levels of triglycerides (TG), total cholesterol (TC), glucose, insulin, leptin, liver enzymes, malondialdehyde (MDA), furthermore insulin resistance and (sterol regulatory element-binding protein-1c) SREBP-1c were detected. Levels of high-density lipoprotein cholesterol (HDL-C), adiponectin, superoxide dismutase (SOD), catalase (CAT), and PPAR-α (peroxisome proliferator-activated receptor-α) considerably decreased. Treatment by betanin, particularly the 20 mg/kg dosage, attenuated these changes. CONCLUSION: Betanin is a potential treating agent of steatohepatitis and works through up-regulation of PPAR-α, down-regulation of SREBP-1c, modification of adipokine levels and modulation of lipid profile.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Chemical modification of bacterial alpha-amylases: changes in tertiary structures and the effect of additional calcium.

A comparative study was performed on the effect of calcium on native and chemically modified forms of mesophilic and thermophilic alpha-amylases. Circular dichroism (CD) and irreversible thermoinactivation studies were carried out in the absence and presence of 10 mM calcium. From the CD experiments, changes in the tertiary structure of these enzymes, brought about by modification, were concluded. Furthermore, these changes were found to be influenced by the presence of calcium. Sorbitol was very effective in affording protection against irreversible thermoinactivation of native and modified forms of the enzymes, both in the absence and presence of calcium. Results are discussed in terms of the usefulness of this new approach involving a combination of medium and chemical modification for protein stabilization and enhancement of catalytic potential.