Hispidin-enriched Sanhuangporus sanghuang ethanolic extract: A novel GLP-1 inducer with non-mutagenic properties.

While traditionally valued for its medicinal properties, studies on Sanghuangporus sanghuang have mainly focused on its α-glucosidase inhibition and polysaccharides. This pioneering study presents four significant innovations in antidiabetic research. First, we report an unprecedented breakthrough in hispidin production, achieving a concentration of 287.3 mg/g in the S. sanghuang ethanol extract (GKSSEt), which represents a substantial increase over conventional preparations. Second, hispidin-enriched GKSSEt showed no evidence of genotoxicity under the Ames test, in vitro mammalian chromosome aberration test, and in vivo mammalian erythrocyte micronucleus test, following OECD guidelines. Third, we unveil antidiabetic mechanisms through comprehensive molecular investigations, demonstrating hispidin-enriched GKSSEt's action in stimulatin GLP-1 secretion. Fourth, our molecular docking analyses reveal previously unreported binding interactions, with fasciculine A, hypholomine B, and inoscavin A showing superior affinities to GLP-1 receptor. Our research positions hispidin-enriched GKSSEt as a promising therapeutic candidate and suggests a novel strategy for diabetes management through the synergistic action of concentrated bioactive compounds.