LAUSR

Seven new coumarin analogues (1, 2, and 4-8), together with ten known analogues (3, 9-17), were isolated from the air-dried pericarp of Citrus grandis. The structures of these compounds were determined by HR-ESI-MS, UV/vis, and 1D- and 2D-NMR spectra. Meanwhile, the hepatoprotective activities of all these coumarins were evaluated by MTT assays using the d-galactosamine-induced LO2 cell injury model. The results show that compounds 3 and 4 exhibited the strongest hepatoprotective activities. Moreover, compounds 3 and 4 suppressed increases in the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in d-galactosamine-treated LO2 cells, further confirming the hepatoprotective effects of these compounds. Mechanistically, compounds 3 and 4 increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the level of malondialdehyde (MDA) in injured LO2 cells induced by d-galactosamine. These findings shed light on a better understanding of the hepatoprotective effect of Citrus grandis, providing novel insights into the development of coumarin-based hepatoprotective drugs in the future.