# Mangiferin as a Novel In Vitro Polyphenolic Inhibitor of Amyloid Aggregation

## TL;DR

Mangiferin, a natural compound, was found to inhibit amyloid aggregation in lab tests, showing potential for treating neurodegenerative diseases like Alzheimer's.

## Contribution

Mangiferin is identified as a novel polyphenolic inhibitor of amyloid aggregation with multitargeted effects.

## Key findings

- Mangiferin significantly inhibited Aβ1–42 and Cterm_mutA aggregation in a concentration-dependent manner.
- Mangiferin altered aggregation mechanisms by forming larger oligomers in Aβ1–42 and reducing oligomer size in Cterm_mutA.
- Mangiferin showed no cytotoxicity and reduced amyloid-induced toxicity in SH-SY5Y cells.

## Abstract

Amyloid aggregation is a pathological hallmark of several
neurodegenerative
disorders, including Alzheimer’s disease. Polyphenolic compounds
are emerging as promising candidates for therapeutic intervention
due to their capacity to interfere with multiple stages of amyloidogenesis.
In this study, we investigated, in vitro, the antiamyloidogenic
potential of mangiferin (MGF), a xanthonoid polyphenol
with established pharmacological activity but previously unexplored
in the context of amyloid modulation. Using a combination of biophysical,
spectroscopic, and microscopic techniques, we assessed the effects
of MGF on the aggregation behavior of two distinct amyloidogenic
peptides: Aβ1–42 and Cterm_mutA. Thioflavin
T (ThT) assays revealed that MGF significantly inhibited
aggregation in a concentration-dependent manner, with maximal inhibition
at a 1:5 peptide:MGF ratio. Nanoparticle tracking analysis
(NTA) and microscopy studies demonstrated peptide-specific differences
in the mechanism of action of MGF: MGF promoted
the formation of larger, nonfibrillar oligomers in Aβ1–42, while it reduced oligomer size in Cterm_mutA. This effect was most
likely attributable to the disruption of π–π interactions.
Importantly, MGF exhibited no cytotoxicity in SH-SY5Y
cells and significantly attenuated the amyloid-induced toxicity of
both peptides. These findings highlight MGF as a promising,
multitargeted modulator of amyloid aggregation with potential applications
in neuroprotection and the development of novel antiamyloid therapies