Chemical synthesis, isolation, purification and in vivo properties of anthocycanins - FRQNT-Team supplements grant

阿尔茨海默病（AD）是全世界最严重的社会经济和医疗负担之一。在加拿大，大约有75万人患有痴呆症（约占65岁以上人口的7%），其总成本估计为122亿美元（约占加拿大GDP的1%）。随着65岁以上人群中阿尔茨海默病患病率每5年翻一番，这一负担正在不断增加。目前对阿尔茨海默病的治疗只有症状，只有25-50%的患者对这些治疗有反应。我们和其他人已经证明，一些天然可用的多酚化合物可以有效地预防大脑甚至肠-脑轴的多种AD致病机制。我们最近开发了一种专有配方（MAF14001），包含四种特定的多酚，是治疗AD的良好候选药物。我们的研究结果表明，MAF14001配方的使用限制了空间记忆的下降。然而，血浆浓度仍然相对较低且变化很大，这对有效的多酚类治疗构成了障碍。这些观察结果与广泛的观察结果一致，即由于生理环境中的化学不稳定和吸收不良，多酚的生物利用度是其功效的常见限制。

Alzheimer's disease (AD) is one of the most severe socio-economical and medical burdens worldwide. In Canada, around 750,000 people are affected by dementia (~7% of people aged 65+ years) and its overall cost is estimated to $Bn 12.2 (~1% of Canada GDP). This burden is constantly growing as prevalence of AD doubles every 5 years among people aged 65+ years. Current treatment for AD are only symptomatic and only 25-50% of patients respond to these treatments. We and others have demonstrated that some naturally available polyphenolic compounds could efficiently prevent multiple AD pathogenic mechanisms in the brain and even through the gut-brain axis. We have recently developed a proprietary formulation (MAF14001) of four specific polyphenols that showed to be a good candidate as treatment for AD. Our results suggest that the administration of MAF14001 formulation limits the spatial memory decline. However, the plasma concentrations remained relatively low and varied considerably, constituting an obstacle to efficacious polyphenols-based treatment. These observations are aligned with widespread observations that bioavailabity of polyphenols is a common limitation to their efficacy, due to chemical unstability in physiological environment and poor absorption. To remediate these issues, several strategies have already been tested successfully, particularly the incorporation of the phenolic compounds into emulsions to decrease their degradations throughout the gastro-intestinal tract and increase their absorption. Double emulsions of "Water-in-Oil-in-Water" (W1/O/W2) type are the best suited candidates for effective delivery of the polyphenolic compound. Therefore, we hypothesize that the incorporation of the formulation MAF14001 into a food-grade double-emulsion will enhance the bioaccessibility, the absorption and thus its effects on cognitive function of an AD mouse model.