Evaluation of molecular mechanisms responsible for in vivo anti-Alzheimer’s property of Euphorbia cotinifolia methanol extract

Alzheimer's is considered as the most prevalent neurological disease; it is a degenerative and progressive disease that affects brain’s neurons causing memory, language and thinking loss, as well as behavioral abnormalities. This study was performed to assess the anti-Alzheimer features of Euphorbia cotinifolia methanol extract (ECM). Antioxidant activity was performed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and high-performance liquid chromatography (HPLC) was performed to identify some constituents present in ECM. Aluminum chloride-induced Alzheimer's Wistar rats were used to access the therapeutic potential of ECM. Several behavioral experiments were conducted to assess the impact of ECM treatment on motor dysfunction and cognitive abilities. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) studies were conducted to explore the effect of ECM treatment of different biomarkers. Half-maximal inhibitory concentration (IC50) of ECM and standard (ascorbic acid) in DPPH assay was found to be 18.61 and 11.37 µg/mL, respectively. The HPLC confirms the presence of chlorogenic acid, gallic acid, caffeic acid, sinapic acid, quercetin, and benzoic acid in ECM. Data from in vivo behavioral studies showed a significant improvement in motor dysfunctions and cognitive abilities of animals treated with ECM. ECM treatment also elevated the acetylcholine, superoxide dismutase, catalases, glutathione peroxidase, and glutathione levels. Histopathological examination showed a reduction in neurofibrillary tangles and neuronal loss. qPCR studies showed reduced expression of interleukins (IL-1-α, IL-1-β), tumor necrosis factors (TNF-α and TNF-β) secretase in ECM-treated groups. Findings of the current study highlight the anti-Alzheimer’s potential of E. cotinifolia.