Phytosterols disaggregate bovine serum albumin under the glycation conditions through interacting with its glycation sites and altering its secondary structure elements

Discovering small molecules with protein-disaggregation effects is recently needed. For the first time, we in-tensely studied the anti-amyloidogenic effects of 3 structurally different phytosterols (PS), namely stigmasterol, beta-sitosterol, and gamma-oryzanol, on bovine serum albumin (BSA) under aggregations-promoting conditions using multispectral, microstructure, and molecular docking methods. Results found that PS dose-and structure- de-pendently inhibited BSA-aggregations under the glycation conditions through separating BSA-peak size, quenching Tryptophan-intensity, altering BSA-hydrophobicity, and microstructural declining the aggregates of glycated-BSA. Throughout the underlying mechanism beyond its disaggregation effects, PS reformed cross-beta-sheet structure, SDS-PAGE-bands, and XRD-peaks of glycated-BSA aggregates. Most importantly, PS were found to bind with some lysyl and arginine glycation sites of BSA, specifically Lys114, Lys116, Lys136, Lys431, Arg427, and Arg185, via Hydrogen-bonding with their -OH-groups and pi-pi interactions of their steroid core. Taken together, the current results unleash that PS could restrict BSA-aggregations under the glycation conditions and their subsequent changes, which can assist in the design of reasonable therapeutics.