title: Bacoside-A, an Indian Traditional-Medicine Substance, Inhibits β-Amyloid Cytotoxicity, Fibrillation, and Membrane Interactions.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ravit
authors.initials: R
authors.lastname: Malishev
authors.affiliation: 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.
authors.forename: Shira
authors.initials: S
authors.lastname: Shaham-Niv
authors.affiliation: 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.
authors.forename: Sukhendu
authors.initials: S
authors.lastname: Nandi
authors.affiliation: 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.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.affiliation: 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.
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
authors.affiliation: 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.
authors.forename: Raz
authors.identifier: 0000-0002-0336-1384
authors.initials: R
authors.lastname: Jelinek
mesh_terms: D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D007194:India; D008519:Medicine, Traditional / Q000379:methods; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000187:drug effects* / Q000378:metabolism*; D066263:Protein Aggregation, Pathological; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012503:Saponins; D014315:Triterpenes; C075222:amyloid beta-protein (1-42); C500175:bacoside A
keywords: amyloid−membrane interactions; bacoside-A; fibrillation inhibitors; fluorescence anisotropy; giant vesicles; β-Amyloid; β-amyloid oligomers