Identification of Hypoglycemic and Antioxidant Components From Malus micromalus Makino Fruits With Potential for Functional Food Applications

Malus micromalus Makino, a fruit crop with a millennium‐long cultivation heritage in China, has hitherto received limited systematic investigation regarding its bioactive principles and the mechanistic underpinnings of its glucose‐modulating effects. Sixteen compounds were isolated and structurally identified from the fruit. The bioactive components and action modes were systematically explored via network pharmacology, in vitro bioassays, enzyme kinetics, molecular simulation, and in vivo validation. ESR1 and MAPK3 were predicted as potential hub targets involved in insulin resistance and oxidative stress regulation. Oleanolic acid, ursolic acid, and hyperoside exhibited dual functional activities, with potent α‐glucosidase inhibitory effects (IC ₅₀ = 0.037, 0.038, and 0.047 mM, respectively) stronger than acarbose in this yeast‐derived enzyme assay system, plus remarkable DPPH, and ABTS ⁺ radical scavenging capacities. Enzyme kinetic analysis demonstrated a noncompetitive inhibition mode, with unchanged K _m value, and dose‐dependently decreased V _max . Molecular docking indicated that OA and UA had high binding affinities with ESR1 and MAPK3. Notably, 100‐ns molecular dynamics simulation suggested that OA could form sustained hydrogen bonds with ESR1 and maintain the structural stability of the receptor–ligand complex. Within the in vivo setting, OA treatment at 25 and 50 mg/kg engendered dose‐dependent improvements in systemic glucose handling, peripheral insulin sensitivity, and circulating lipid profiles among HFD‐induced obese animals. Collectively, this study clarifies the bioactive constituents and metabolic regulatory effects of M. micromalus Makino, and provides scientific evidence for its development as a functional food ingredient for glycemic management.

Practical Applications

The present findings offer direct translational value for the functional food sector. The potent α‐glucosidase inhibitory activity of oleanolic acid (OA, IC ₅₀ = 0.037 mM)—surpassing acarbose by approximately sevenfold—positions M. micromalus fruit extracts as promising candidates for glycemic‐management food ingredients. Given its noncompetitive inhibition kinetics, OA retains efficacy irrespective of carbohydrate load, a critical advantage for incorporation into staple foods with variable starch content. From a formulation standpoint, the ethyl acetate fraction enriched in triterpenoids and flavonoids could be developed as standardized extracts for functional beverages, bakery products, or nutraceutical capsules. The established industrial processing of M. micromalus into fruit wine and preserves further supports scalable valorization. However, the poor aqueous solubility of pentacyclic triterpenoids necessitates future work on delivery systems (e.g., nano‐emulsions or liposomal encapsulation) to enhance bioavailability and thermal stability during food processing. In addition, the dual antioxidant–hypoglycemic profile of these constituents suggests potential as multifunctional natural preservatives that simultaneously extend shelf life and confer metabolic health benefits. Subsequent studies should evaluate the sensory impact, storage stability, and consumer acceptability of M. micromalus ‐fortified food prototypes.