Hesperidin abrogates bisphenol A endocrine disruption through binding with fibroblast growth factor 21 (FGF-21), α-amylase and α-glucosidase: an in silico molecular study

BACKGROUND: Fibroblast growth factor 21 (FGF-21), alpha-amylase, and alpha-glucosidase are key proteins implicated in metabolic dysregulations. Bisphenol A (BPA) is an environmental toxicant known to cause endocrine dysregulations. Hesperidin from citrus is an emerging flavonoid for metabolic diseases management. Through computational approach, we investigated the potentials of hesperidin in abrogating BPA interference in metabolism. The 3D crystal structure of the proteins (FGF-21, α-amylase, and α-glucosidase) and the ligands (BPA and hesperidin) were retrieved from the PDB and PubChem database respectively. Using Autodock plugin Pyrx, molecular docking of the ligands and individual proteins were performed to ascertain their binding affinities and their potentials to compete for the same binding site. Validation of the docking study was considered as the ability of the ligands to bind at the same site of each proteins. The docking poses were visualized using UCSF Chimera and Discovery Studio 2020, respectively to reveal each of the protein-ligands interactions within the binding pockets. Using SwissAdme and AdmeSar servers, we further investigated hesperidin's ADMET profile. Hesperidin used was purchased commercially. RESULTS: Hesperidin and BPA competitively bound to the same site on each protein. Interestingly, hesperidin had greater binding affinities (Kcal/mol) - 5.80, - 9.60, and - 9.60 than BPA (Kcal/mol) - 4.40, - 7.20, - 7.10 for FGF-21, α-amylase, and α-glucosidase respectively. Visualizations of the binding poses showed that hesperidin interacted with stronger bonds than BPA within the proteins' pockets. Although hesperidin violated Lipinski rule of five, this however can be optimized through structural modifications. CONCLUSIONS: Hesperidin may be an emerging natural product with promising therapeutic potentials against metabolic and endocrine derangement.