Guaianolide sesquiterpenoids from Ainsliaea yunnanensis.

Six previously undescribed C17-guaianolides, a previously undescribed guaianolide alkaloid, and two previously undescribed guaianolides as well as 10 known guaianolides were obtained from an ethanol extract of Ainsliaea yunnanensis Franch. The chemical structures of all previously reported sesquiterpenoids were determined by extensive NMR spectroscopic analysis in combination with a modified Mosher's method. All isolates were in vitro screened for inhibitory effect against nitric oxide release in RAW 264.7 macrophages stimulated by LPS. Zaluzanin C remarkably inhibited the production of nitric oxide with an IC50 value of 6.54 µM.

Cytotoxic and Anti-inflammatory Sesquiterpenes from Ainsliaea henryi.

Three new sesquiterpenoids, 4α-hydroxyeudesm-11(13)-en-12-yl 3-methylbutanoate (1), diaspanolide E (2), and (13α)-germacra-1(10),4-dien-12,8α-olid-15-oic acid (3), along with eight known sesquiterpenoids (4 - 11), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 - 3 were elucidated by spectroscopic analysis (1D-, 2D-NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC50 value of 6.54 ± 0.16 µm. Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC50 value of 2.2 ± 0.2 µm.

Terpenoids from Ainsliaea latifolia and their cytotoxic activities.

Two new compounds including one new sesquiterpenoid and one new monoterpenoid, together with 10 known compounds were isolated from the whole plants of Ainsliaea latifolia. The structures of these compounds were elucidated by analysis of spectroscopic data. All compounds were evaluated for their cytotoxic activities.

Abieslactone induces cell cycle arrest and apoptosis in human hepatocellular carcinomas through the mitochondrial pathway and the generation of reactive oxygen species.

Abieslactone is a triterpenoid lactone isolated from Abies plants. Previous studies have demonstrated that its derivative abiesenonic acid methyl ester possesses anti-tumor-promoting activity in vitro and in vivo. In the present study, cell viability assay demonstrated that abieslactone had selective cytotoxicity against human hepatoma cell lines. Immunostaining experiments revealed that abieslactone induced HepG2 and SMMC7721 cell apoptosis. Flow cytometry and western blot analysis showed that the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and p21, and down-regulation of CDK2 and cyclin D1. Furthermore, our results revealed that induction of apoptosis through a mitochondrial pathway led to upregulation of Bax, down-regulation of Bcl-2, mitochondrial release of cytochrome c, reduction of mitochondrial membrane potential (MMP), and activation of caspase cascades (Casp-9 and -3). Activation of caspase cascades also resulted in the cleavage of PARP fragment. Involvement of the caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. Recent studies have shown that ROS is upstream of Akt signal in mitochondria-mediated hepatoma cell apoptosis. Our results showed that the accumulation of ROS was detected in HepG2 cells when treated with abieslactone, and ROS scavenger partly blocked the effects of abieslactone-induced HepG2 cell death. In addition, inactivation of total and phosphorylated Akt activities was found to be involved in abieslactone-induced HepG2 cell apoptosis. Therefore, our findings suggested that abieslactone induced G1 cell cycle arrest and caspase-dependent apoptosis via the mitochondrial pathway and the ROS/Akt pathway in HepG2 cells.