Pyridocarbazole alkaloids from Ochrosia borbonica: lipid-lowering agents inhibit the cell proliferat

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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.
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