Malishev Ravit, Shaham-Niv Shira, Nandi Sukhendu, Kolusheva Sofiya, Gazit Ehud, Jelinek Raz
Department of Chemistry, and §Ilse Katz Institute for Nanotechnology, Ben Gurion University of the Negev , Beer Sheva 84105, Israel.
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, and ∥Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University , Tel Aviv 69978, Israel.
ACS Chem Neurosci. 2017 Apr 19;8(4):884-891. doi: 10.1021/acschemneuro.6b00438. Epub 2017 Jan 30.
Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aβ42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, preincubation of bacoside-A with Aβ42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles. In parallel, spectroscopic and microscopic analyses reveal that bacoside-A blocked membrane interactions of Aβ42, while formation of Aβ42 oligomers was not disrupted. These interesting phenomena suggest that inhibition of Aβ42 oligomer assembly into mature fibrils, and blocking membrane interactions of the oligomers are likely the underlying factors for ameliorating amyloid toxicity by bacoside-A and its putative physiological benefits.
从假马齿苋植物中提取的一类化合物——印度人参皂苷A，是一种被认为具有治疗特性的民间药物，尤其能增强认知功能和改善记忆力。我们发现，印度人参皂苷A对细胞毒性、纤维化，特别是对淀粉样β蛋白（1-42）（Aβ42）的膜相互作用具有显著的抑制作用，该肽在阿尔茨海默病的进展和毒性中起重要作用。具体而言，将印度人参皂苷A与Aβ42预孵育，在缓冲溶液中，更显著的是在膜囊泡存在的情况下，均能显著降低细胞毒性并抑制纤维形成。同时，光谱和显微镜分析表明，印度人参皂苷A阻断了Aβ42的膜相互作用，而Aβ42寡聚体的形成未受干扰。这些有趣的现象表明，抑制Aβ42寡聚体组装成成熟纤维以及阻断寡聚体的膜相互作用，可能是印度人参皂苷A改善淀粉样毒性及其假定生理益处的潜在因素。
