In traditional Arabian medicine, the Rhus tripartita plant (family Anacardiaceae) has been used to treat inflammatory conditions. Although Rhus extracts have been reported for their cardioprotective effects, information regarding their active principle compounds remains insufficient. The present investigation was aimed at determining the antioxidant chemical constituents of the methanolic extract of R. tripartita stem bark and evaluating their ability to ameliorate methylglyoxal-induced endothelial cell apoptosis. Ten flavonoid compounds (1–10) were isolated and identified using DPPH radical scavenging bioassay-guided chromatographic separation. A new proanthocyanidin (rhuspartin) (1) was isolated and identified as 3,5,13,14-flavantetrol-(4β→8)-catechin, using extensive spectroscopic data and high resolution-mass spectrometry. Among the compounds (1, 5, 7–10) tested for toxicity toward cultured endothelial cells (HUVECs), the non-cytotoxic compounds 1 and 7 evinced cytoprotective potential that reversed the methylglyoxal-induced apoptosis (by 62% and 64%, respectively) through downregulation of caspase 3/7. © 2019

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