Activités anticholinestérasique, neuroprotectrice et neuroregénératrice de l’extrait hydroéthanolique d’Autranella congolensis (sapotaceae)

Abstract

Due to progressive population aging, the incidence of aging-related diseases, especially Alzheimer’s disease characterized by progressive cognitive decline is increasing. There has been emerging evidence on the link of certain dietary components, particularly polyphenols, to brain wellness and cognitive outcomes. The objective of this thesis was to evaluate the modulative effects of Autranella congolensis, on biochemical, neuropathological and cognitives alterations implicated in AD development. Firstly, three extracts were prepared (aqueous, ethanolic and hydroethanolic) from bark of A. congolensis and their total phenolics, flavonoids contents were determined by colorimetric tests. The antioxidant potential of these plant extracts was also evaluated. We further characterized the best extract using liquid chromatographic coupled with mass spectrometry technics (HPLC/MS). Secondly, we evaluated biological activities of best extract on parameters involved in the development of the AD (oxidative stress, brain metabolic dysfunction, neurodegeneration, cognitive decline). In order to accomplish these, the AlCl3 rats model that develops pathologic processes close to what is observed in AD was used. The hydroethanolic extract (HEEAC) showed more polyphenols (28.77±2.39 mgEAG/g DM) and flavonoids (14.93±0.133 mgEQ /g DM). This extract also showed the best in vitro antioxidant activity and was therefore used for the rest of the study. We identified three compounds in this extract: catechin, ferulic acid and taraxerol (known as neuroprotector and neuromodulator). All those compounds were previously isoled from this plant. In vivo, HEEAC (150 mg/kg) significantly (p < 0,05) prevents the formation of conjugated diene, generation of MDA and accumulation of oxidized proteins induced by AlCl3 better than vitamin E. This effect was the result of modulation of brain antioxidant enzyme activities (catalase and glutathione peroxidase). HEEAC also prevents the hyperactivity of brain cholinesterase, lowering brain cholesterol, improve brain glucose utilization by increasing glycolysis and Krebs cycle and improve calcium homeostasis by increasing the enzymatic activities of ion pumps. Futhermore, the HEEAC co-administration resulted in preservation of neuronal morphology of hippocampus layers and in conservation of memory abilities. Taken together, these results show that HEAAC could be a relevant therapeutic agent to prevent or at least slow down the evolution of the pathology in Alzheimer’s disease.