Bioactivity-Guided Isolation of Potential Antidiabetic and Antihyperlipidemic Compounds from Trigonella stellata

The in vitro antidiabetic and antihyperlipidemic activities of an alcoholic extract of Trigonella stellata were evaluated in terms of the activation of PPAR_α and PPAR_γ in human hepatoma (HepG2) cells. The extract was investigated phytochemically, aiming at the isolation of the most active compounds to be used as a platform for drug discovery. Three new isoflavans, (3S,4R)-4,2′,4′-trihydroxy)-7-methoxyisoflavan (1), (3R,4S)-4,2′,4′-trihydroxy-7-methoxy-4′-O-β-d-glucopyranosylisoflavan (2), and (2S,3R,4R)-4,2′,4′-trihydroxy-2,7-dimethoxyisoflavan (3), were isolated and characterized along with the five known compounds p-hydroxybenzoic acid (4), 7,4′-dihydroxyflavone (5), dihydromelilotoside (6), quercetin-3,7-O-α-l-dirhamnoside (7), and soyasaponin I (8). The structures of 1–3 were elucidated using various spectroscopic techniques including HRESIMS and 1D and 2D NMR. The absolute stereochemistry of the new isoflavans (1–3) was determined using both experimental and calculated electronic circular dichroism as well as DP4 calculations. The isolated compounds were tested for their PPAR_α and PPAR_γ activation effects in HepG2 cells.