Essential Oil of Acorus tatarinowii Schott Ameliorates Aß-Induced Toxicity in Caenorhabditis elegans through an Autophagy Pathway.

BACKGROUND: Acorus tatarinowii Schott [Shi Chang Pu in Chinese (SCP)] is a traditional Chinese medicine frequently used in the clinical treatment of dementia, amnesia, epilepsy, and other mental disorders. Previous studies have shown the potential efficacy of SCP against Alzheimer's disease (AD). Nevertheless, the active constituents and the modes of action of SCP in AD treatment have not been fully elucidated. PURPOSE: The aim of this study was to investigate the protective effects of SCP on abnormal proteins and clarify its molecular mechanisms in the treatment of AD by using a Caenorhabditis elegans (C. elegans) model. METHODS: This study experimentally assessed the effect of SCP-Oil in CL4176 strains expressing human Aß in muscle cells and CL2355 strains expressing human Aß in pan-neurons. Western blotting, qRT-PCR, and fluorescence detection were performed to determine the oxidative stress and signaling pathways affected by SCP-Oil in nematodes. RESULTS: SCP-Oil could significantly reduce the deposition of misfolded Aß and polyQ proteins and improved serotonin sensitivity and olfactory learning skill in worms. The analysis of pharmacological action mechanism of SCP-Oil showed that its maintaining protein homeostasis is dependent on the autophagy pathway regulated partly by hsf-1 and sir-2.1 genes. CONCLUSION: Our results provide new insights to develop treatment strategy for AD by targeting autophagy, and SCP-Oil could be an alternative drug for anti-AD.

Anti-Aß single-chain variable fragment antibodies exert synergistic neuroprotective activities in Drosophila models of Alzheimer's disease.

Both active and passive immunotherapy protocols decrease insoluble amyloid-ß42 (Aß42) peptide in animal models, suggesting potential therapeutic applications against the main pathological trigger in Alzheimer's disease (AD). However, recent clinical trials have reported no significant benefits from humanized anti-Aß42 antibodies. Engineered single-chain variable fragment antibodies (scFv) are much smaller and can easily penetrate the brain, but identifying the most effective scFvs in murine AD models is slow and costly. We show here that scFvs against the N- and C-terminus of Aß42 (scFv9 and scFV42.2, respectively) that decrease insoluble Aß42 in CRND mice are neuroprotective in Drosophila models of Aß42 and amyloid precursor protein neurotoxicity. Both scFv9 and scFv42.2 suppress eye toxicity, reduce cell death in brain neurons, protect the structural integrity of dendritic terminals in brain neurons and delay locomotor dysfunction. Additionally, we show for the first time that co-expression of both anti-Aß scFvs display synergistic neuroprotective activities, suggesting that combined therapies targeting distinct Aß42 epitopes can be more effective than targeting a single epitope. Overall, we demonstrate the feasibility of using Drosophila as a first step for characterizing neuroprotective anti-Aß scFvs in vivo and identifying scFv combinations with synergistic neuroprotective activities.

Effect of bushenyisui formula on brain tissue apoptosis and Bcl-2 in beta-amyloid protein-induced Alzheimer's disease rat models.

OBJECTIVE: To investigate the effect of Bushenyisui Formula on cell apoptosis and positive B cell lymphoma (Bcl-2) in the Brain of rat models of Alzheimer's disease (AD) induced by beta-amyloid protein (Abeta) and the mechanism underlying the effect. METHODS: Total of 40 SD rats, 20 females and 20 males, were randomly assigned to 4 groups, controlled group (A), model group (B), conventional treatment group (C) and Bushenyisui Formula treatment (BYFT) group (D), 10 rats in each group. Abeta 1-42 was injected into the bilateral hippocampus of the rats in group B, C and D to create the models of AD. Sham operation was performed on the rats of group A in the same way by injecting equal volume of 0.9% sodium chloride solution into their bilateral hippocampus. 5 days after operation, Bushenyisui Formula was intraperitoneally administered at a dose of 450 mg/kg to the rats of group D (QD) for 20 days. Equal volume of 0.9% sodium chloride solution was intraperitoneally injected into the rats of group B with the same procedure. C suspension (20 mg/mL) was intraperitoneally injected into the rats of group B with the same procedure. The number of apoptotic cells in Brain and the positive Bcl-2 were counted. The changes of learning and memory abilities were evaluated using Y-maze. RESULTS: Right after the establishment of the models, group B, C and D compared to group A respectively, the outcomes of Y-maze were significantly different from that of group A, which suggested obvious learning and memory disorder in those groups (P < 0.01). After treatment, the times of electronic shocks of group C and D were significantly less than that of group B (P < 0.05), and the numbers of apoptotic cells and positive Bcl-2 were significantly different from those of group B, apoptotic sells' number of group C and D smaller than that of group B and the number of positive Bcl-2 greater than that of group B. CONCLUSION: Bushenyisui Formula could increase the number of Bcl-2 in brain, which improved the function of nervous system pertaining to learning and memory abilities.

Ameliorative effect of 1,2-benzenedicarboxylic acid dinonyl ester against amyloid beta peptide-induced neurotoxicity.

Amyloid beta peptide (Abeta)-induced oxidative stress may be linked to neurodegenerative disease. Ethanol extracts of Rosa laevigata protected PC12 cells from hydrogen peroxide-induced oxidative stress. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with R. laevigata extract. The effect of R. laevigata on oxidative stress-induced cell death was further investigated by lactate dehydrogenase release assays and trypan blue exclusion assays. Administration of 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract to mice infused with Abeta significantly reversed learning and memory impairment in behavioural tests. After behavioural testing, the mice were sacrificed and brains were collected for the examination of lipid peroxidation, catalase activity and acetylcholinesterase (AchE) activity. These results suggest that 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract may be able to reduce Abeta-induced neurotoxicity, possibly by reducing oxidative stress. Therefore, R. laevigata extract may be useful for the prevention of oxidative stress-induced neurodegenerative disorders.

Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease.

Increasing evidence suggests that Alzheimer's disease (AD) is associated with oxidative damage that is caused in part by mitochondrial dysfunction. Here we investigated the feasibility of modifying Alzheimer pathology with the mitochondrial antioxidant coenzyme Q (CoQ). Exogenous CoQ protected MC65 neuroblastoma cells from amyloid-beta protein precursor C-terminal fragment (APP CTF)-induced neurotoxicity in a concentration dependent manner, with concentrations of 6.25 microM and higher providing near complete protection. Dietary supplementation with CoQ at a dose of 10 g/kg diet to C65/Bl6 mice for one month significantly suppressed brain protein carbonyl levels, which are markers of oxidative damage. Treatment for one month with 2 g lovastatin/kg diet, which interferes with CoQ synthesis, resulted in a significant lowering of brain CoQ10 levels. Mitochondrial energetics (brain ATP levels and mitochondrial membrane potential) were unaffected by either CoQ or lovastatin treatment. Our results suggest that oral CoQ may be a viable antioxidant strategy for neurodegenerative disease. Our data supports a trial of CoQ in an animal model of AD in order to determine whether a clinical trial is warranted.