摘要
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 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50(28)0.41 and 0.92μmol·L^–1,respectively)and lower triglyceride levels by 50%-60%at the concentration of 1μmol·L^–1,being more potent than the positive drug luteolin(EC50(28)2.63μmol·L–^1).A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA,which consequently inhibited the mitotic clonal expansion of 3 T3-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 d evelopment of anti-obesity drugs.
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 3 T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation(EC50（28） 0.41 and 0.92 μ mol·L–1, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μ mol·L–1, being more potent than the positive drug luteolin(EC50（28） 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 3 T3-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 d evelopment of anti-obesity drugs.
基金
supported by the National Natural Science Foundation of China(Nos.81573302,81722042,and 81703336)
the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2014A0303 06047)
the Science and Technology Planning Project of Guangdong Province,China(No.2015A020211007)
the Fundamental Research Funds for the Central Universities(No.17ykzd12)
the Guangdong Provincial Key Laboratory of Construction Foundation(No.2017B030314030)
