Lupeol from Nyctanthes arbor-tristis Inhibits Matrix Metalloproteinase Activity, Angiogenesis and Proliferation of Glioma Cells

Abstract

Angiogenesis plays a critical role in cancer progression and, hence, inhibiting angiogenesis is considered as a key strategy in cancer therapy. In this study, we screened the antiangiogenic and cytotoxic properties of Nyctanthes arbor-tristis Linn. plant of family Oleaceae, which is used in traditional medicine for the treatment of cancer, arthritis and inflammation. The antiangiogenic activity of ethanolic extract of Nyctanthes arbor-trsitis (ENA) was assessed using Chick Chorioallantoic Membrane (CAM) assay. The mechanism of antiangiogenic action was evaluated via gelatin digestion assay for matrix metalloproteinase (MMP) inhibitory activity. Cytotoxic activity of the extract on glioma cells was assessed using MTT and trypan blue dye exclusion assays. ENA impaired capillary formations in chick CAM model and inhibited MMPactivity on gelatin gels in a concentration dependent manner. The extract was found to be cytotoxic on glioma cells at higher concentrations. Bioactivity guided purification of ENA using column chromatography and thin layer chromatography afforded lupeol as the active principle. Lupeol exhibits significant MMPinhibitory activity at a concentration of 2 μg/mL and cytotoxic activity on glioma with an IC₅₀ value of 10.75 μg/mL. The results of this study hold promise for developing this plant as a source of lupeol, a highly bioactive compound against angiogenesis.