In this study, the aerial parts of mature Vietnamese Euphorbia tithymaloides plants were put through cytotoxic, anti-diabetic, and phytocompositional evaluations. Specifically, four extracts (petroleum ether (PE), ethyl acetate (EA), methanol (Me), and aqueous (W)) were prepared by maceration at room temperature. All extracts, together with some isolated compounds, were investigated for cytotoxicity against some human normal and cancer cell lines (fibroblasts, HeLa, NCI-H460, HepG2, MCF-7, and Jurkat) using the standardized modified sulforhodamine B (SRB) assay. Additionally, the anti-diabetic activity of extracts and compounds was evaluated via their α-glucosidase inhibitory capacity. The obtained results indicated that Vietnamese E. tithymaloides extracts exhibited moderate cytotoxic activity, among which the PE extract possessed the highest values, on the NCI-H460 cell line. Second, the aqueous extract was revealed to possess very high α-glucosidase inhibitory activity (IC50 = 113.75 ± 14.02 μg ml-1). From the PE extract, three new jatrophane diterpenoids (named tithymal A, tithymal B, and tithymal C) and two known ones were isolated and structurally elucidated using NMR and MS spectroscopies. Noticeably, tithymal A exhibited significantly high inhibitory activity against α-glucosidase (IC50 = 10.71 ± 0.52 μg ml-1). These observations have significantly highlighted the medicinal potential of Vietnamese E. tithymaloides and expanded its scientific fascination.
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