New diterpenoids and cytotoxic and anti-inflammatory diterpenoids from Amentotaxus formosana.

Two new abietane diterpenoids, ramentoxide (1) and ramentoxidone (2) and a new icetexane diterpenoid, amentonone (3) were isolated from the barks of Amentotaxus formosana. The structures of 1-3 were determined by spectroscopic methods. Known compounds brevitaxin (4), and (+)-ferruginol (5) and ent-kaur-16-en-15-one (6) isolated from this plant revealed potent cytotoxic activity against human breast adenocarcinoma cells, MCF-7 cells with an IC(50) value of 0.08 ± 0.05 µg/mL, and significant anti-inflammatory activities, respectively.

Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of Hep 3B cells.

Bufotalin is one of the bufadienolides isolated from Formosan Ch'an Su, which is made of the skin and parotid glands of toads. Ingestion of toad venom results in severe morbidity and high mortality. Although Ch'an Su is clinically toxic, it has been used as an important traditional Chinese medicine for heart failure and pains. In this study, bufotalin-induced apoptosis in human hepatocellular carcinoma Hep 3B cells was investigated. The results indicate that externalization of phosphatidylserine, accumulation of sub-G(1) cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells. The signaling pathway might be via the activation of caspase-8, increase in mitochondrial tBid, disruption of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF). Active caspase-8 might activate caspase-9 and caspase-3 leading to the cleavage of nuclear PARP. Presence of AIF and cleaved PARP in the nuclei might lead to DNA fragmentation. Caspase-8 inhibitor (Z-IETD) or wide-ranging caspase inhibitor (Z-VAD) significantly suppressed the bufotalin-induced apoptosis, while the anti-Fas neutralization antibody had no effect. These data suggest that bufotalin-induced apoptosis in Hep 3B cells might involve caspases and AIF.

Cytotoxic prenylflavonoids from Artocarpus elasticus.

Five new prenylated flavonoids, artelastoheterol (1), artelasticinol (2), cycloartelastoxanthone (3), artelastoxanthone (4), and cycloartelastoxanthendiol (5), along with five known compounds, were isolated from the root bark of Artocarpus elasticus. The structures of 1-5 were elucidated by spectroscopic methods and through comparison with data reported in the literature. The previously known compound artonol A (6) exhibited cytotoxic activity against the A549 human cancer cell line, with an ED50 value of 1.1 microg/mL.

Constituents of the pericarp of Garcinia subelliptica.

A new benzophenone, garcinielliptone FA (1), and a new benzoylphloroglucinol, garcinielliptone FB (2), along with six known compounds, were isolated from the pericarp of Garcinia subelliptica. The structures and relative configurations of 1 and 2 were elucidated by spectroscopic methods and supported by computer-generated molecular modeling. Compound 2 exhibited cytotoxic activity against several human cancer cell lines.

Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide.

Supercritical carbon dioxide (SC-CO2) was used as the elution solvent for fractioning ethanolic extract (E) of Cordyceps sinensis (CS), a traditional Chinese herbal remedy, into R, F1, F2, and F3 fractions. This extractive fractionation method is amenable to large scale and is nontoxic. These four fractions were characterized in terms of total polysaccharides and cordycepin concentrations, scavenging ability of free radicals, and anti-tumor activities. Experimental results demonstrated that fractionation altered the distributions of total polysaccharides and cordycepin in fractions. Fraction R was the most active fraction to scavenge free radicals and inhibit the proliferation of carcinoma cells, followed by the fraction F1 and the extract E. The effect of scavenging on 1,1-diphenyl-2-picryl hydrazyl (DPPH) of CS extract and fractions at 2 mg/ml was R (93%), F1 (75%), E (66%), F2 (47%), and F3 (27%). The IC50 (50% cell growth inhibitory concentration) of tumor cell proliferation and colony formation on human colorectal (HT-29 and HCT 116) and hepatocellular (Hep 3B and Hep G2) carcinoma cells by fraction R were around 2 microg/ml. Conversely, R did not affect the growth of normal dividing human peripheral blood mononuclear cells (PBMC) by exhibiting a large value of IC50 over 200 microg/ml. Accumulation of tumor cells at sub-G1 phase and the fragmentation of DNA, typical features of programmed cell death, were observed in a time and dose dependent manner. Scavenging of free radicals and anti-cancer activity (value of IC50) correlated closely with the quantities of polysaccharides (Spearman's rho=0.901 and -0.870, respectively). Taken together, our findings suggest that fraction R, obtained by SC-CO2 fluid extractive fractionation, showed strong scavenging ability and selectively inhibited the growth of colorectal and hepatocellular cancer cells by the process of apoptosis.

New alkaloids and a tetraflavonoid from Cephalotaxus wilsoniana.

A new homoerythrina alkaloid, C-3-epi-wilsonione (1), a new tetraflavonoid, taiwanhomoflavone C (2), and a new stereoisomer of desmethylcephalotaxinone (3) have been isolated from the leaves and heartwood of Cephalotaxus wilsoniana, respectively. The structures were elucidated by spectroscopic methods. Compound 1 showed cytotoxic activity against a number of human cancer cell lines in vitro.

Potent cytotoxic lignans from Justicia procumbens and their effects on nitric oxide and tumor necrosis factor-alpha production in mouse macrophages.

A new lignan glycoside, 4-O-alpha-L-arabinopyranosyl-(1' "-->2' ')-beta-D-apiofuranosyldiphyllin (2), named procumbenoside A, and 11 known compounds were isolated from the whole plant of Justicia procumbens. The structure of 2 was established by spectral analysis and chemical methods. The known compounds justicidin A (1), diphyllin (3), and tuberculatin (4) showed potent cytotoxic effects against a number of cancer cells in vitro. Compounds 1 and 4 also strongly enhanced tumor-necrosis factor-alpha (TNF-alpha) generation from mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS).