Pyridocarbazole alkaloids from Ochrosia borbonica: lipid-lowering agents inhibit the cell proliferation and adipogenesis of 3T3-L1 adipocyte via intercalating into supercoiled DNA.
10.1016/S1875-5364(19)30080-9
- Author:
Yao-Hao XU
1
;
Wei LI
1
;
Yong RAO
2
,
3
;
Zhi-Shu HUANG
1
;
Sheng YIN
4
Author Information
1. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
2. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: raoyong0805@
3. com.
4. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: yinsh2@mail.sysu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Lipid-lowering agents;
Ochrosia borbonica;
Pyridocarbazole alkaloids
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(9):663-671
- CountryChina
- Language:English
-
Abstract:
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 (EC = 0.41 and 0.92 μmol·L, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μmol·L, being more potent than the positive drug luteolin (EC = 2.63 μmol·L). 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.
