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

Publication date: September 2019Source: Chinese Journal of Natural Medicines, Volume 17, Issue 9Author(s): Yao-Hao XU, Wei LI, Yong RAO, Zhi-Shu HUANG, Sheng YINAbstractBioassay-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.
Source: Chinese Journal of Natural Medicines - Category: Complementary Medicine Source Type: research