Phytochemicals Characterization and Antidiabetic Efficacy of <i>Muntingia calabura</i> L. Leaves Extract: In vitro and in vivo Studies

Abstract

Background: Muntingia calabura L. leaves are traditionally used in West Java to manage hyperglycemia, yet integrated evidence linking their chemical profile with bioactivity remains limited. Objectives: To profile secondary metabolites in M. calabura leaf extract (MCLE), evaluate antioxidat capacity, and perform an assessment of antihyperglycemic efficacy in a diabetic rat model. Methods: Muntingia calabura L. leaves extract was characterized by ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC–HRMS/MS). Antioxidant activity was measured using the ABTS•⁺ decolorization assay. Antihyperglycemic activity was evaluated in streptozotocin (STZ)-induced diabetic rats treated orally with MCLE (125 or 250 mg/kgBW) for 14 days. Fasting blood glucose (FBG), 2-hour postprandial glucose (2hPP), and body weight were analyzed using two-way repeated-measures analysis of variance (ANOVA). Results: Ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry annotated diverse secondary metabolites, with the most intense signals assigned to 5-hydroxy-6,7-dimethoxy-2-phenyl-4H-chromen-4-one (19.99%), isokaempferide (16.94%), and scrophulein (10.90%). Muntingia calabura L. leaves extract and its n-hexane and ethyl acetate fractions exhibited ABTS•⁺ radical scavenging activity. In STZ-induced rats, significant group × day interactions were observed for all outcomes (P < 0.001). The 250 mg/kgBW dose attenuated diabetes-associated weight loss and reduced FBG (P < 0.01), and 2hPP at this dose (134.0 ± 4.0 mg/dL) was not significantly different from the normal control or glibenclamide groups (P > 0.05). Conclusions: Muntingia calabura L. leaves extract demonstrated antihyperglycemic activity in STZ-induced diabetic rats, improving both FBG and 2hPP alongside measurable antioxidant capacity.