Growing Conditions Drive Variation in Charantin and Momordicine Content and In Vitro Glucose-Regulating Activities of Thai Bitter Melon (Momordica charantia L.)

Bitter melon (Momordica charantia L.) is widely used as an antidiabetic food and traditional remedy, but the causes of variation in its bioactive content remain unclear. This study aimed to investigate whether genotype or growing conditions are the primary determinants of this variation. ITS barcoding identified all ten accessions as M. charantia, but genetic relationships only partly corresponded to agricultural classification and did not predict chemotypes. The native Pathum Thani genotype was grown at four sites, and charantin content varied ninefold (2.56–23.73 mg/100 mg extract), exceeding the range observed among the ten accessions and showing a negative correlation with soil pH. In addition, fertilizer form affected the two markers in opposite ways: manure alone maximised charantin, whereas manure plus 15-15-15 fertilizer maximised momordicine, suggesting a potential trade-off between the sterol and cucurbitane biosynthetic pathways. Charantin was as potent as acarbose in inhibiting α-glucosidase and α-amylase, extract potency correlated with charantin content, and consensus docking predicted that the glucosyl moiety was positioned near the catalytic residues. In streptozotocin-injured β-cells, charantin conferred stronger cytoprotection, whereas momordicine induced the highest insulin release. The native Pathum Thani extract was consistently the most active, including in assays of myotube glucose uptake. Standardised bitter melon products therefore require both charantin and momordicine as quality-control markers, together with controlled cultivation practices, rather than selection based solely on agricultural classification.