👤 Fils Armand Ella

The pathogenesis of Alzheimer's disease (AD) is complex, involving multiple interrelated pathways. Consequently, developing multi-target-directed ligands may represent an effective therapeutic strategy. This study investigates the anti-Alzheimer potential of two biflavonoids isolated from Allanblackia floribunda against monoamine oxidase A (MAO-A), β-secretase (BACE-1), and glycogen synthase kinase-3β (GSK-3β), three key enzymes implicated in AD progression. The biflavonoids, (2S,3S)-volkensiflavone-7-O-β-glucopyranoside (1) and (2R,3S)-volkensiflavone-7-O-β-D-acetylglucopyranoside (2), were purified and structurally identified using spectroscopic methods. Enzymatic fluorimetric assays were conducted to assess their inhibition of MAO-A, BACE-1, and GSK-3β. The mode and reversibility of inhibition were characterized for both compounds, confirming them as potent MAO-A inhibitors. In silico simulations were performed on the three enzymes to gain insights into their interactions and modes of action. Compounds 1 and 2 were found to be reversible and moderately selective MAO-A inhibitors with IC Show less

Alzheimer's disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer's disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer's disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats. The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl A phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of β-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aβ. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl TEF of TeMac™ displays a potential ability to inhibit the activities of β-secretase, monoamine oxidase, and Aβ fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers. Our findings indicate that TEF of TeMac™ prevents Alzheimer's-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment. Show less