Cucurbitane-Type Glycosides and Sterol from Momordica balsamina Linn. As Target Potential Leads for Diabetes Management

Momordica balsamina Linn. is widely used in traditional medicine for the management of diabetes; however, the specific bioactive compounds responsible for this activity have not been fully isolated and structurally elucidated from South African populations. This study reports, for the first time, the isolation and comprehensive characterization of antidiabetic compounds from South African samples of M. balsamina. Crude extracts were obtained through sequential solvent extraction, followed by isolation and purification using vacuum liquid chromatography. Structural elucidation was achieved using HPLC, UPLC–MS, FTIR, and NMR spectroscopy. The antidiabetic potential of the isolated compounds was evaluated through inhibition assays against α-amylase, α-glucosidase, and β-glucosidase. Molecular docking was employed to examine binding interactions with these target enzymes, while cytotoxicity was assessed using the MTT assay against Vero and HEK-293 cell lines. Two compounds, DD26.27 and EAEA1.2, were successfully isolated from dichloromethane and ethyl acetate extracts, respectively. Both compounds demonstrated concentration-dependent inhibition of the tested enzymes. Notably, molecular docking revealed strong binding affinities and favorable interactions with key catalytic residues, surpassing the standard drug acarbose and corroborating the in vitro results. Cytotoxicity studies confirmed that, at lower concentrations, the compounds were non-toxic to the tested cell lines. Collectively, these findings provide novel scientific validation of the traditional use of M. balsamina in South Africa and identify promising lead compounds for further in vivo studies and antidiabetic drug development targeting postprandial hyperglycemia.