CN: 32-1845/R
ISSN: 2095-6975
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XU Yao-Hao, LI Wei, RAO Yong, HUANG Zhi-Shu, YIN Sheng. Pyridocarbazole alkaloids from Ochrosia borbonica: li-pid-lowering agents inhibit the cell proliferation and adipogenesis of 3T3-L1 adipocyte via intercalating into supercoiled DNA[J]. Chinese Journal of Natural Medicines, 2019, 17(9): 663-671

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

XU Yao-Hao, LI Wei, RAO Yong, HUANG Zhi-Shu, YIN Sheng
Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China
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.
Key words:    Ochrosia borbonica    Pyridocarbazole alkaloids    Lipid-lowering agents   
Received: 2019-04-28   Revised:
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