4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Molecular Biology Division, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
J Alzheimers Dis. 2018;64(3):787-800. doi: 10.3233/JAD-170862.
Natural products are a significantly underutilized source of potential treatments against human disease. Alzheimer's disease (AD) is a prime example of conditions that could be amenable to such treatments as suggested by recent findings.
Aiming to identify novel potentially therapeutic approaches against AD, we assessed the effects of Cichorium spinosum and Sideritis scardica extracts, both distinct components of the Mediterranean diet.
METHODS/RESULTS: After the detailed characterization of the extracts' composition using LC-HRMS methods, they were evaluated on two AD neuronal cell culture models, namely the AβPP overexpressing SH-SY5Y-AβPP and the hyperphosphorylated tau expressing PC12-htau. Initially their effect on cell viability of SH-SY5Y and PC12 cells was examined, and subsequently their downstream effects on AβPP and tau processing pathways were investigated in the SH-SY5Y-AβPP and PC12-htau cells. We found that the S. scardica and C. spinosum extracts have similar effects on tau, as they both significantly decrease total tau, the activation of the GSK3β, ERK1 and/or ERK2 kinases of tau, as well as tau hyperphosphorylation. Furthermore, both extracts appear to promote AβPP processing through the alpha, non-amyloidogenic pathway, albeit through partly different mechanisms.
These findings suggest that C. spinosum and S. scardica could have a notable potential in the prevention and/or treatment of AD, and merit further investigations at the in vivo level.
天然产物是治疗人类疾病的潜在药物的重要来源，但尚未得到充分利用。阿尔茨海默病（AD）就是一个很好的例子，最近的研究结果表明，这种疾病可以通过这种治疗方法来缓解。
为了寻找针对 AD 的新型潜在治疗方法，我们评估了两种地中海饮食的特有成分——菊苣和山小橘的提取物的作用。
方法/结果：使用 LC-HRMS 方法详细分析了提取物的组成后，我们在两种 AD 神经元细胞培养模型上评估了它们的作用，即过表达 AβPP 的 SH-SY5Y-AβPP 和过度磷酸化 tau 表达的 PC12-htau。首先，我们检测了提取物对 SH-SY5Y 和 PC12 细胞活力的影响，然后在 SH-SY5Y-AβPP 和 PC12-htau 细胞中研究了它们对 AβPP 和 tau 处理途径的下游影响。我们发现，山小橘和菊苣的提取物对 tau 具有相似的作用，因为它们都能显著降低总 tau、GSK3β、ERK1 和/或 ERK2 激酶的激活以及 tau 的过度磷酸化。此外，这两种提取物似乎都能通过非淀粉样蛋白形成途径促进 AβPP 的加工，尽管它们的作用机制部分不同。
这些发现表明，菊苣和山小橘可能在预防和/或治疗 AD 方面具有显著的潜力，值得在体内水平进一步研究。
