Title:Cytotoxic Sesquiterpenes from Sonchus oleraceus
Volume: 20
Issue: 6
Author(s): Hongying Zhang, Yiding Wang, Shaojiu Wang, Qian Wang, Tianjing Wang, Jie Zhu*Bing Liu
Affiliation:
- Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang,China
Keywords:
Sonchus oleraceus, chemical constituent, sesquiterpene, cytotoxicity, apoptosis, Bax/caspase-9.
Abstract:
Background: Sonchus oleraceus is a large and widespread plant in the world. It is edible to humans
as a leaf vegetable and is also used as a folklore medicinal herb in the treatment of infections and inflammatory
disease, but limited research on its chemical constituents has been done.
Objective: To isolate and identify the bioactive ingredients from S. oleraceus.
Methods: 20kg of S. oleraceus was extracted twice with 75% alcohol. The concentrated extract was suspended
in H2O and partitioned with petroleum ether, dichloromethane, ethyl acetate and n-butanol, respectively. The
ethyl acetate phase was subjected to repeated normal chromatography on a silica gel column chromatography
and eluted with a gradient of CH2Cl2-MeOH to give 12 crude fractions. Fraction 6 was subjected to ODS silica
gel column chromatography, Sephadex LH-20 and HPLC to yield 1 and 2. Cell viability of 1 and 2 on A549,
H292 and Caco2 cell lines were assayed by MTT method. Apoptosis analysis and apoptosis related proteins
were detected subsequently.
Results: Two new sesquiterpenes were isolated from S. oleraceus and identified by NMR spectra and HR-ESIMS.
1 selectively suppressed the viability of A549 and H292 cells with IC50 values of 14.2, and 19.5μM respectively,
while possessing no cytotoxicity against Caco2 cells (IC50 > 100μM). 2 did not exhibit cytotoxicity
against A549, H292 and Caco2 cells (IC50 > 100μM). 1 significantly decreased the density of live cells and
could cause cell apoptosis at 10 and 20μM in a dose-dependent manner. After treatment of 1 for 24h, the level of
cleaved caspase-3 was increased accompanied by the reduction in procaspase-3 expression, and the downregulation
of Bcl-2 was associated with the enhancement of Bax expression. 1 could lead to the up-regulation of
cytochrome c and activation of caspase-9.
Conclusion: 1 and 2 are new sesquiterpenes from S. oleraceus. 1 could induce apoptosis in A549 and H292
cells through Bax/caspase-9 pathway.
