Diverse metabolites from corn silk with anti-Aβ_1-42 aggregation activity

Area of Science:

• Natural Product Chemistry
• Neuroscience
• Medicinal Chemistry

Background:

• Corn silk (Stigma maydis) is a traditional remedy with potential therapeutic properties.
• Amyloid-beta (Aβ) aggregation is a hallmark of Alzheimer's disease pathology.
• Identifying natural inhibitors of Aβ aggregation is crucial for developing new Alzheimer's treatments.

Purpose of the Study:

• To isolate and characterize compounds from corn silk.
• To evaluate the inhibitory effects of these compounds on Aβ aggregation.
• To explore the structure-activity relationships of enantiomers in inhibiting Aβ aggregation.

Main Methods:

• Isolation of compounds using High-Performance Liquid Chromatography (HPLC) with chiral columns.
• Structure elucidation via comprehensive spectroscopic analyses (NMR) and quantum chemical calculations (ECD).
• In vitro evaluation of Aβ aggregation inhibition and molecular docking simulations.

Main Results:

• Five pairs of enantiomeric compounds, including seven new ones, were isolated from corn silk.
• Compounds 4a, 4b, and a known compound demonstrated significant inhibition of Aβ aggregation, outperforming curcumin.
• Enantiomers 4a and 4b exhibited distinct inhibition profiles, explained by docking studies.

Conclusions:

• Corn silk is a valuable source of bioactive compounds with potential therapeutic applications.
• Compounds 4a and 4b are potent inhibitors of Aβ aggregation, offering a basis for further drug development.
• The study highlights the importance of enantiomeric separation and evaluation in drug discovery.