Anti-Hyperglycemic Effects of Alpha-Mangostin in Animal Models: A Systematic Review and Meta-Analysis

Diabetes mellitus, particularly type 2 diabetes mellitus, is a growing global health burden characterized by chronic hyperglycemia and insulin resistance. Alpha-mangostin (AM), a xanthone from Garcinia mangostana pericarp, exhibits antioxidant, anti-inflammatory, and metabolic regulatory properties in preclinical models. We performed a systematic review and meta-analysis of controlled in vivo studies to assess AM's anti-hyperglycemic effects. Fourteen studies (25 comparisons) in rodent models of diabetes or hyperglycemia were included. Primary outcome was blood glucose; secondary outcomes were glycated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Random-effects meta-analysis demonstrated that AM significantly reduced fasting blood glucose (mean difference (MD) = -8.75 mmol/L; 95% CI: -10.73 to -6.78; p < 0.001) and HbA1c (MD = -2.20%; 95% CI: -3.07 to -1.32; p < 0.001). AM did not significantly alter circulating insulin (Hedges' g = 0.43; 95% CI: -0.62 to 1.49; p = 0.42) but improved insulin resistance as measured by HOMA-IR (MD = -0.90; 95% CI: -1.68 to -0.12; p = 0.02). Subgroup, sensitivity, and risk-of-bias analyses supported the robustness of the glucose-lowering association, although substantial between-study heterogeneity was present. Overall, this study provides preclinical evidence that AM exerts significant antihyperglycemic and insulin-sensitizing effects, supporting its potential as a multitarget metabolic modulator. Further standardized and mechanistically informed studies are warranted to facilitate translational progression.