# Study on the Competitive Substitution of Four Polyphenolic Compounds on the HSA-Bound α-Zearalenol In Vitro Simulated Modeling

## TL;DR

This study shows that certain plant compounds can displace a harmful mycotoxin from binding to a key blood protein, potentially reducing its toxicity.

## Contribution

The study demonstrates competitive displacement of α-ZOL by polyphenols from HSA, offering a novel detoxification mechanism.

## Key findings

- Polyphenols bound HSA more tightly than α-ZOL, reducing its binding affinity.
- Quercetin and baicalin were the most effective in displacing α-ZOL from HSA.
- Polyphenols altered the protein microenvironment, affecting α-ZOL binding.

## Abstract

α-Zearalenol (α-ZOL), the primary metabolite of zearalenone (ZEN), is a prevalent mycotoxin in agricultural products (e.g., corn, wheat) and poses health risks due to its toxicity. However, strategies to mitigate its toxicity are needed. Therefore, this study aims to determine whether selected polyphenols (quercetin, baicalin, rosmarinic acid, naringenin) can competitively displace α-ZOL from human serum albumin (HSA) and to clarify the interaction mechanisms. The results showed that competitive interactions between α-ZOL, HSA, and the polyphenols were observed. The polyphenols bound HSA more tightly than α-ZOL (higher Ka) and significantly reduced α-ZOL’s Ka, indicating direct competition. Moreover, as evidenced by synchronous fluorescence, the polyphenols altered the microenvironments of tyrosine and tryptophan residues, directly impacting α-ZOL binding. The HPLC-ultrafiltration results revealed that the polyphenols tested competitively displaced α-ZOL from HSA, with the relative potency of quercetin ≈ baicalin > rosmarinic acid > naringenin. Collectively, our competitive binding assays demonstrate that quercetin, baicalin, rosmarinic acid, and naringenin competitively displace α-ZOL from its binding site(s) on HSA. Thus, our study not only suggests a novel mechanism to alleviate the toxicity of ZEN and α-ZOL but also provides a scientific basis for developing dietary interventions against these mycotoxins.