Coumarin Analogues from the Citrus grandis (L.) Osbeck and Their Hepatoprotective Activity

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.