Evaluating the therapeutic efficacy of phytochemicals in ameliorating cytotoxic effects of amyloid beta

Abstract

AbstractBackgroundThere is lack of reliable treatment approaches to combat early cognitive impairment, as well as Alzheimer’s disease (AD). Since AD is a multifactorial disease, therapeutic approaches must be targeted on disease specific multiple‐biochemical pathways. There is a need to explore and test alternative disease modifiers which can target multiple metabolic pathways i.e., phytochemicals to combat such perturbations. This project will identify bioenergetic and viability changes that occur in response to amyloid pathology in cell models. Further, the therapeutic potential of a set of phytochemicals (safranal, berberine, taxifolin, bilobalide and vinpocetine) will be evaluated in mitigating such changes.MethodNeuroblastoma cell lines SH‐SY5Y cells and BE (2)‐M17 have been used to model AD in vitro. They were differentiated into mature human neurons using 10 µM retinoic acid. Amyloid beta 1‐42 (Ab42) is being used to induce neurotoxicity in the cells, which will be followed by treatment with phytochemicals. MTT (3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide) assay and flow cytometry will be used to evaluate cell viability, followed by sea horse assay to evaluate the oxygen consumption rate. Confocal microscopy will be used to confirm the images of amyloidosis and will be compared with the phytochemically treated group and the control group. Western blotting will be used to study the targeted pathways and proteins.ResultDifferentiation of the cells have been successfully accomplished and confirmed through morphological changes in the cells. Treatment with Ab42 is currently under progress, which will be followed by treatment with phytochemicals. The protective effect of the phytochemicals will be evaluated through MTT, and sea horse assays and pathways will be studied using western blotting.ConclusionThis project will help to evaluate the therapeutic potential of selected phytochemicals, and thereby help to inform future pre‐clinical and clinical studies.