Screening of a Fraction with Higher Amyloid β Aggregation Inhibitory Activity from a Library Containing 210 Mushroom Extracts Using a Microliter-Scale High-Throughput Screening System with Quantum Dot Imaging

Summary

Researchers screened 210 mushroom species from Japan to find those that could prevent harmful protein clumping in the brain associated with Alzheimer’s disease. They identified a purified fraction from the mushroom Elfvingia applanata that was more effective than a known anti-Alzheimer’s compound at stopping these protein clumps from forming. The extract also protected nerve cells from damage in laboratory tests. This finding suggests mushrooms could potentially be developed into a functional food to help prevent Alzheimer’s disease.

Background

Alzheimer’s disease is a prevalent neurodegenerative disorder characterized by amyloid plaques formed from amyloid β (Aβ) aggregation. Current FDA-approved Aβ-targeting antibody drugs have limited efficacy and significant side effects. Mushrooms are medicinal fungi with various bioactive compounds that have shown potential neuroprotective properties.

Objective

To evaluate the Aβ aggregation inhibitory activity of 210 mushroom species from Hokkaido, Japan using a microliter-scale high-throughput screening (MSHTS) system with quantum dot nanoprobes, and to identify and purify the most active fraction.

Results

Eleven mushroom extracts showed high Aβ aggregation inhibitory activity (EC50 <50 µg/mL). The ethyl acetate extract of Elfvingia applanata (t037) was selected for further purification, yielding fraction 5 (f5) with the highest inhibitory activity (EC50 2.30 µg/mL), superior to rosmarinic acid (EC50 10.7 µg/mL). f5 also inhibited Aβ deposition on SH-SY5Y cell surfaces and showed evidence of synergistic compound interactions.

Conclusion

Fraction f5 from Elfvingia applanata demonstrates superior Aβ aggregation inhibitory activity with potential as a functional food for Alzheimer’s disease prevention. Further investigation of the synergistic mechanisms between multiple compounds in f5, along with in vivo testing, safety assessment, and bioavailability studies, is necessary for therapeutic development.
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