Abstract
Type 2 diabetes mellitus remains a major global health challenge, and natural hypoglycemic compounds are of increasing interest. Aqueous extracts from five Brazilian medicinal plants (Lippia origanoides Kunth, Amburana cearensis (Allemão) A.C. Smith, Justicia pectoralis Jacq., Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz, and Spondias mombin L.) were evaluated for α-glucosidase and intestinal disaccharidase inhibition; next, they were chemically profiled by UPLC-HRMS. Extracts of L. origanoides, A. cearensis, and J. pectoralis exhibited the strongest activities, attributed to flavonoids, iridoid and cinnamic acid derivatives, phenolic acids, and saponins. Molecular docking identified hyperoside, eudesmic acid and isoquercitrin as their main α-glucosidase inhibitors, respectively. In vitro testing confirmed that isoquercitrin effectively inhibited α-glucosidase (IC(50) = 0.09 mg mL(-1)), showing stronger activity than acarbose. ADME simulations indicated low gastrointestinal absorption but favorable intestinal enzyme-targeted properties, consistent with their pharmacological profiles. Acute toxicity in zebrafish showed low toxicity for L. origanoides and A. cearensis and moderate levels for J. pectoralis, supporting their overall safety. These findings highlight these species as promising sources of bioactive compounds for developing safe, plant-based antidiabetic agents.