Mechanistic insights into the antioxidant activity of sorghum bran phenolics via compositional profiling, network pharmacology and molecular docking

Sorghum bran contains diverse phenolic compounds with potent antioxidant activity that contributes to their health-promoting effects in humans. However, the considerable diversity of its phenolic compounds makes it challenging to elucidate their regulatory mechanisms on biological pathways in vivo, and their roles in oxidative stress-related diseases remain poorly understood. Herein, this work aimed to investigate how phenolic compounds from sorghum bran may exert antioxidant effects through specific biological pathways using integrative in silico analyses. To achieve this, the phenolic composition of five sorghum bran genotypes was analyzed using HPLC-DAD-ESI-QTOF-MS/MS. Potential in vivo antioxidant mechanisms and key phenolic compounds involved in oxidative stress-related diseases were predicted by integrating network pharmacology and molecular docking. The results showed that the predicted antioxidant-associated targets modulated by phenolics were mainly enriched in cancer-related pathways, especially the PI3K-AKT signaling pathway. Eleven key phenolic compounds were screened, which potentially inhibit the PI3K-AKT signaling pathway through interactions with core targets in the pathway (Src, AKT1, and EGFR) and regulators involved in pathway crosstalk (ERα, and MAPK1), respectively. This study established a hypothesis for future in vivo research on the precise mechanisms by which sorghum bran phenolics exert their antioxidant effects.