Inhibitory effects of three genuine resin glycosides from Calystegia hederacea on in vitro porcine lipase assay and in silico docking simulation analysis

Resin glycosides are characteristically present in Convolvulaceae plants. We recently demonstrated that three genuine resin glycosides, muricatins V, VI, and IX, from the seeds of Ipomoea muricata, inhibit lipase. This study investigated whether the resin glycoside fraction (CHRG Fr.) obtained from the whole plants of Calystegia hederacea and three resin glycosides, calyhedins II (1), III (2), and VIII (3), from the rhizomes of this plant, can inhibit porcine lipase in vitro. The results indicated the inhibitory effects of CHRG Fr. (IC₅₀; 33.1 µg/mL) and 1-3 (IC₅₀; 4.5-23.7 µM). In silico molecular docking simulations revealed that 1-3 bind stably to the catalytic sites of porcine (PDB ID: 1ETH) and human (PDB ID: 1LPB) pancreatic lipases. Using data from 1 to 3 and three muricatins that we had previously determined, we observed a high correlation (R² = 0.817, log₁₀ (a; IC₅₀ value) = 0.472799 x (b; docking score) + 5.9412, n = 6) between in vitro IC₅₀ values and in silico binding scores for porcine lipase. By a leave-one-out cross-validation approach, we confirmed that this equation is a useful model with moderate predictive performance. There was also a high correlation (R² = 0.928) in binding scores between porcine and human lipases. In conclusion, this study is the first to demonstrate that 1-3 from C. hederacea can inhibit porcine lipase in vitro and bind stably to lipase catalytic sites in silico. Therefore, it is suggested that resin glycosides from C. hederacea may serve as unique lipase inhibitors. (246 words).