Pyridocarbazole alkaloids from Ochrosia borbonica: li-pid-lowering agents inhibit the cell proliferation and adipogenesis of 3T3-L1 adipocyte via intercalating into supercoiled DNA

Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids, ellipticine ( 1 ) and 9-methoxyellipticine ( 2 ), and six known monoterpenoid indole alkaloids ( 3-8 ). Lipid-lowering assay in 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC₅₀=0.41 and 0.92 μmol·L^-1, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μmol·L^-1, being more potent than the positive drug luteolin (EC₅₀=2.63 μmol·L^-1). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-L1 cells at the early differentiation phase, leading to the retardance of following adipogenesis and lipogenesis. These findings suggest that 1 and 2 may serve as promising leads for further development of anti-obesity drugs.