Medvedeva Maria, Kitsilovskaya Natalia, Stroylova Yulia, Sevostyanova Irina, Saboury Ali Akbar, Muronetz Vladimir
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia.
Department of Systems Biology, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia.
Biomedicines. 2022 Sep 12;10(9):2255. doi: 10.3390/biomedicines10092255.
Earlier we showed that derivatives of hydroxycinnamic acids prevent amyloid transformation of alpha-synuclein and prion protein. The aim of this work was to determine the content of 3-hydroxycinnamic acid derivatives in coffee extracts and to evaluate their activity in relation to alpha-synuclein amyloid aggregation. Hydroxycinnamic acid derivatives were identified in aqueous and ethanol extracts of coffee beans by quantitative mass spectrometric analysis. Only 3,4-dimethoxycinnamic acid (13-53 μg/mL) was detected in significant amounts in the coffee extracts, while ferulic acid was present in trace amounts. In addition, 3-methoxy-4-acetamidoxycinnamic acid (0.4-0.8 μg/mL) was detected in the roasted coffee extracts. The half-maximum inhibitory concentrations of alpha-synuclein fibrillization reaction in the presence of coffee extracts, as well as inhibitory constants, were determined using thioflavin T assay. The inhibitory effect of black and green coffee extracts on alpha-synuclein fibrillization is dose-dependent, and in a pairwise comparison, the constants of half-maximal inhibition of fibrillization for green coffee extracts are comparable to or greater than those for black coffee. Thus, coffee extracts prevent pathological transformation of alpha-synuclein in vitro, probably due to the presence of 3,4-dimethoxycinnamic acid in them. Consequently, coffee drinks and coffee extracts can be used for the prevention of synucleinopathies including Parkinson's disease.
我们之前的研究表明，羟基肉桂酸衍生物可防止α-突触核蛋白和朊病毒蛋白发生淀粉样变。本研究的目的是测定咖啡提取物中3-羟基肉桂酸衍生物的含量，并评估其对α-突触核蛋白淀粉样聚集的活性。通过定量质谱分析在咖啡豆的水提取物和乙醇提取物中鉴定出羟基肉桂酸衍生物。在咖啡提取物中仅检测到大量的3,4-二甲氧基肉桂酸（13 - 53μg/mL），而阿魏酸含量微量。此外，在烘焙咖啡提取物中检测到3-甲氧基-4-乙酰氨基氧基肉桂酸（0.4 - 0.8μg/mL）。使用硫黄素T测定法测定了在咖啡提取物存在下α-突触核蛋白纤维化反应的半数最大抑制浓度以及抑制常数。黑咖啡和绿茶提取物对α-突触核蛋白纤维化的抑制作用呈剂量依赖性，并且在成对比较中，绿茶提取物纤维化半数最大抑制常数与黑咖啡相当或更高。因此，咖啡提取物可能由于其中存在3,4-二甲氧基肉桂酸而在体外防止α-突触核蛋白的病理转化。因此，咖啡饮品和咖啡提取物可用于预防包括帕金森病在内的突触核蛋白病。
