This study investigated the potential of scale-up mango leaf extract (MLE) as a treatment for diabetes, a global public health concern. MLE was prepared by boiling in water, yielding 12.07% (w/w), with a bioactive mangiferin content of 165.67 ± 10.88 μg/g in the crude powder. Mechanistically, MLE demonstrated a hypoglycemic effect by stimulating glucagon-like peptide-1 (GLP-1) secretion in NCI-H716 L-cells. This occurred through activation of the MAPK signaling pathway, evidenced by increased p-ERK1/2, p-p38, and p-c-Jun expression, and the Wnt signaling pathway, shown by increased β-catenin and decreased GSK-3β and Axin1 expression, consistent with molecular docking. In a type 2 diabetic rat model, MLE administration (40 mg/kg) significantly reduced metabolic parameters, including fasting blood glucose (FBG), body weight, cholesterol (CHOL), triglycerides (TGs), and HbA1c. Notably, MLE lowered serum insulin and the HOMA-IR index, and reduced serum dipeptidyl peptidase-IV (DPP-IV) levels, resulting in increased serum GLP-1, comparable to the drug sitagliptin. These findings suggest that MLE has great potential to lower blood glucose by inducing GLP-1 secretion via MAPKs and Wnt signaling pathways, positioning it as a promising candidate for alternative diabetes treatment or development as a dietary supplement.

Standardization of Garcinia mangostana L. products is often hindered by the use of toxic solvents and prolonged chromatographic run times. This study presents a sustainable, Green Analytical Chemistry (GAC)-compliant approach for the simultaneous multi-analyte profiling of seven bioactive xanthones (garcinone D, 8-deoxygartanin, γ-mangostin, gartanin, α-mangostin, 9-hydroxycalabaxanthone, and β-mangostin). Optimization of ultrasound-assisted extraction (UAE) identified 100% ethanol as the superior green solvent, achieving exhaustive extraction in only 5 min with a 0.1 g:5 mL mass-to-volume ratio. Separation was optimized by transitioning from a C18 to a C8 stationary phase to reduce hydrophobic retention. Using an isocratic mobile phase of ethanol and 5% acetic acid (62:38, v/v), baseline resolution of all analytes was achieved within 15 min at 254 nm. The method demonstrated high sensitivity with limits of detection (LODs) ranging from 0.5 to 170 ppb and excellent linearity (R2 > 0.999). Precision was confirmed by intra- and inter-day %RSDs < 5.0%. Accuracy was validated via recovery studies (80–120%) in complex matrices, including commercial mangosteen juices and raw pericarps from diverse Thai regions. The environmental impact was quantitatively validated, achieving an AGREE score of 0.74 and a ComplexMoGAPI score of 76. By replacing acetonitrile and methanol with ethanol, this UAE-HPLC method offers a robust, eco-friendly platform for high-throughput routine quality control and phytochemical standardization in the natural product industry.