Cassia tora extract alleviates Aß1-42 aggregation processes in vitro and protects against aluminium-induced neurodegeneration in rats.

OBJECTIVES: To examine the ability of Cassia tora extract to produce, in vitro and in vivo, beneficial effects with respect to events occurring during Alzheimer's disease. METHODS: Previously characterised methanol extract of C. tora was tested for its ability to lessen Aß42 aggregation processes in vitro and to alleviate aluminium-induced impairments in vivo in rats. KEY FINDINGS: Cassia tora extract prevents the aggregation of monomeric, oligomeric and fibrillary Aß1-42 in vitro. Moreover, the daily ingestion of 100 and 400 milligrams of the extract per kilogram of body weight for 60 days ameliorates the neurobehavioral and cognitive abilities of aluminium-treated rats in vivo. Importantly, treatments with the extract trigger a significant recovery of antioxidant enzymes function, a diminution of lipid peroxidation and acetylcholinesterase activity, a decrease of pro-inflammatory cytokines expression and an increase of brain-derived neurotrophic factor levels in both the hippocampus and the frontal cortex. Finally, we evidence that the extract is able to ameliorate the aluminium-dependent loss of neuronal integrity in the CA1 and CA3 regions of the hippocampus. CONCLUSIONS: Altogether, our results reveal that methanol extract of C. tora is able to prevent typical AD-related events and therefore stands as a promising mild and natural anti-AD multitarget compound.

Cassia tora prevents Aß1-42 aggregation, inhibits acetylcholinesterase activity and protects against Aß1-42-induced cell death and oxidative stress in human neuroblastoma cells.

BACKGROUND: Alzheimer's is a complex neurodegenerative disease and is characterized by extraneuronal accumulation of ß-amyloid peptide. Because of its complex nature, multi-target directed ligands (MTDLs) are increasingly being considered as promising anti-Alzheimer therapeutic agents. This study is aimed at determining the effects of Cassia tora ethyl acetate fraction on several Alzheimer-associated deleterious events in test tubes as well as in human neuroblastoma SK-N-SH and SH-SY5Y cell lines. METHOD: Ethyl acetate fraction of C. tora was purified by chromatography, characterized by 1H and 13C NMR, and tested for its ability to prevent Aß 1-42 aggregation by thioflavin-T fluorescence and transmission electron microscopy. We also analyzed the intracellular ROS level and cytotoxicity in SK-N-SH and SH-SY5Y cell lines. RESULTS: The extract inhibits the formation of Aß 1-42 aggregation from monomers and oligomers, as also acetylcholinesterase activity, Aß 1-42 -induced cell death, and Aß 1-42 -dependent intracellular ROS production in both SK-N-SH and SH-SY5Y cells. In-depth chromatographic and spectroscopic analysis of the extract revealed that the active molecules are most likely triglycerides of oleic acid (C18H34O2). CONCLUSION: We demonstrate for the first time that Cassia tora fraction prevents Aß 1-42 aggregation, inhibits acetylcholinesterase and alleviates Aß 1-42 -induced oxidative stress in human neuroblastoma cells. We further suggest the possible use of triglycerides of oleic acid as efficient anti-Alzheimer agents.

Neuro-nutrients as anti-alzheimer's disease agents: A critical review.

Alzheimer's disease (AD) is characterized by a massive neuronal death causing memory loss, cognitive impairment and behavioral alteration that ultimately lead to dementia and death. AD is a multi-factorial pathology controlled by molecular events such as oxidative stress, protein aggregation, mitochondrial dysfunction and neuro inflammation. Nowadays, there is no efficient disease-modifying treatment for AD and epidemiological studies have suggested that diet and nutrition have a significant impact on the development of this disorder. Indeed, some nutrients can protect all kind of cells, including neurons. As prevention is better than cure, life style improvement, with a special emphasis on diet, should seriously be considered as an anti-AD track and intake of nutrients promoting neuronal health is the need of the hour. Diets rich in unsaturated fatty acids, polyphenols and vitamins have been shown to protect against AD, whereas saturated fatty acids-containing diets deprived of polyphenols promote the development of the disease. Thus, Mediterranean diets, mainly composed of fruits, vegetables and omega-3 fatty acids, stand as valuable, mild and preventive anti-AD agents. This review focuses on our current knowledge in the field and how one can fight this devastating neurodegenerative disorder through the simple proper modification of our life style.

Neuroprotective effects of Cassia tora against paraquat-induced neurodegeneration: relevance for Parkinson's disease.

The aim of the present study was to determine whether Cassia tora extracts could reverse the oxidative stress-induced neurodegeneration in a Parkinson's disease in vitro model. The leaves were treated with ethyl acetate (CtEA) or methanol (CtME). The extracts were first analysed by HPLC for their phenolic content and then tested for their neuroprotective effects in human SK-N-SH neuroblastoma cells. Cells were pre-treated with various concentrations of extracts followed by incubation with paraquat (14 µM). Firstly, pre-treatment of SK-N-SH cells with 100 µg/mL of CtEA or CtME significantly reduced the paraquat-induced production of reactive oxygen species. Furthermore, both CtEA and CtME reduced the paraquat-induced apoptosis. Moreover, there was a significant reduction of paraquat-induced DNA damage in SK-N-SH cells pre-treated with CtEA or CtME. Finally, both extracts significantly inhibited paraquat-dependent lipid peroxidation. Altogether, these in vitro data establish C. tora as a possible anti-Parkinson natural remedy.

Activation of α-secretase by curcumin-aminoacid conjugates.

The extracellular senile plaques observed in Alzheimer's disease (AD) patients are mainly composed of amyloid peptides produced from the ß-amyloid precursor protein (ßAPP) by ß- and γ-secretases. A third non-amyloidogenic α-secretase activity performed by the disintegrins ADAM10 and ADAM17 occurs in the middle of the amyloid-ß peptide Aß and liberates the large sAPPα neuroprotective fragment. Since the activation of α-secretase recently emerged as a promising therapeutic approach to treat AD, the identification of natural compounds able to trigger this cleavage is highly required. Here we describe new curcumin-based modified compounds as α-secretase activators. We established that the aminoacid conjugates curcumin-isoleucine, curcumin-phenylalanine and curcumin-valine promote the constitutive α-secretase activity and increase ADAM10 immunoreactivity. Strickingly, experiments carried out under conditions mimicking the PKC/muscarinic receptor-regulated pathway display different patterns of activation by these compounds. Altogether, our data identified new lead natural compounds for the future development of powerful and stable α-secretase activators and established that some of these molecules are able to discriminate between the constitutive and regulated α-secretase pathways.

Molecular studies on Abeta(42) induced genomic instability in aged rabbit brain.

DNA stability and conformation are important in the life cycle of an organism. The DNA instability is postulated to be one of the risk factors for neuronal death in neurodegenerative disorders. Among all other risk factors, amyloid is one of the most important risk factor for neurodegeneration. Abeta(42) is implicated in Alzheimer's disease (AD). Studies from our lab and elsewhere have shown that Abeta(42) could cause DNA damage and alter DNA stability in vitro and there are no mechanistic studies to understand Abeta induced genomic instability under in vivo condition. The present study aims to characterize Abeta(42) induced DNA instability and also to map the changes in DNA conformation in vivo and its correlation to brain structural changes. The aged (4yr) New Zealand rabbits are intracisternally injected with Abeta(42) and are sacrificed after 25 days, when the rabbits developed AD like behavior. Genomic DNA is isolated from frontal cortex (FC), hippocampus (H) and midbrain (M) regions of Abeta(42) injected and control rabbit brain. The DNA stability parameters are analyzed. And the results showed that DNA is damaged in FC and H; where as in M, DNA is in condensed state. The DNA conformation study evidenced the presence of C-, pi- and psi-type DNA in conformations in FC, H and M of Abeta injected rabbit brain regions respectively. But in control rabbit brain, DNA is in B-conformation in all the brain regions studied. Magnetic resonance imaging (MRI) studies showed no significant changes in brain structure between control and Abeta(42) injected aged rabbit brain regions. The mechanism of Abeta(42) induced neurodegeneration through genomic instability is discussed in detail.