Three previously undescribed cucurbitacins J-L (1-3) and two undescribed cucurbitane-type triterpenoid glycosides (4-5) were isolated, along with seven known analogues, from the 95 % ethanol extract of the fruits of Citrullus colocynthis under the guidance of bioassay and molecular networking. The structures of these previously undescribed compounds were elucidated using HRESIMS, 1D and 2D nuclear magnetic resonance data analysis. Absolute configurations were determined through quantum chemical electronic circular dichroism calculations and acid hydrolysis analysis. Compounds 1, 3-4, and 6-11 elicited stimulatory effects on glucagon-like peptide-1 (GLP-1) secretion in Caco-2 cells. Compound 6 has a better effect in promoting GLP-1 secretion at low concentration, with a 1.5-fold changes in GLP-1 secretion compared to the basal group at 5 μM. Compound 8 promoted GLP-1 secretion in a dose-dependent manner, with a 1.54-fold changes in GLP-1 secretion in Caco-2 cells at 20 μM compared to the basal level. These compounds showed the potential to reduce blood glucose levels.
Keywords: Citrullus colocynthis; Cucurbitaceae; Cucurbitacin; Cytotoxicity; GLP-1; Molecular networking.
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