Multi-Target Screening of Anti-Diabetic and Antioxidant Potential Bioactive Constituents from Dandelion

Taraxacum mongolicum Hand.-Mazz (TMHM), a primary source of dandelion, is a globally recognized edible and medicinal plant with significant potential in food, medicine, daily chemical products, and animal husbandry. Although hypoglycemic effects have been reported in other Taraxacum species, the specific hypoglycemic constituents and mechanisms of TMHM are not well understood. The absence of comprehensive multi-target screening methodologies has hindered the elucidation of TMHM's dual inhibitory effects on α-amylase and α-glucosidase, as well as its associated molecular mechanisms. In this study, a multi-target screening strategy was developed to concurrently evaluate α-amylase and α-glucosidase inhibition, integrating multi-target affinity ultrafiltration coupled with ultra-performance liquid chromatography-tandem mass spectrometry (MTAUF-UPLC-MS/MS), molecular docking, and molecular dynamics (MD) simulations. Using this approach, 13 dual-target inhibitors were identified from TMHM. Moreover, at least 5 of these compounds exhibited anti-diabetic activities comparable to the positive control drug acarbose, suggesting that they are principal bioactive constituents responsible for its hypoglycemic effects. Subsequent investigation of the antioxidant capacities of 7 out of the 13 bioactive compounds revealed that most exhibited more potent antioxidant activities than vitamin C (Vc). Based on these findings, molecular docking and MD simulations further validated that quercetin (8) and kaempferol (15), which demonstrated significant hypoglycemic and antioxidant activities, exhibited particularly strong affinities and stable interactions with α-amylase and α-glucosidase, respectively. In conclusion, these findings underscored the considerable potential of TMHM as a natural source of multifunctional bioactive compounds for nutraceutical, functional, and pharmaceutical applications. This study provided a critical foundation for elucidating the mechanisms underlying TMHM's anti-diabetic effects and its therapeutic potential in mitigating diabetes-related complications, thereby facilitating future development and utilization.