Triterpenoid Constituents from the Roots of <i>Paeonia rockii</i> ssp. <i>rockii</i>

An investigation of a chloroform-soluble extract from the roots of Paeonia rockii ssp. rockii yielded three new noroleanane triterpenoids (1–3) together with 19 known compounds. Their structures were established by analysis of the spectroscopic data. The effects of this chloroform-soluble extract and its major constituents on cell proliferation and apoptosis of a panel of human cancer cell lines (melanoma M-14, colon cancer HT-29, breast cancer MCF-7) were evaluated by the MTT bioassay and propidium iodide staining, respectively, in comparison with normal human embryonic kidney cells (HEK-293). Two of the triterpenoids, betulinic acid (4) and oleanolic acid (5), and the crude extract were cytotoxic and induced apoptosis selectively in the M-14 melanoma cell line. This effect was reversed by the caspase-inhibitor z-VAD-fmk, suggesting that such action is mediated by caspase-3 activation

Saponins and Polyphenols from <i>Fadogia ancylantha</i> (Makoni Tea)

Three new saponins (1−3) and a known saponin, together with four known polyphenolic compounds, have been isolated from the fermented and dried leaves of Fadogia ancylantha (Makoni tea). The structures of compounds 1−3 were established by analysis of their spectroscopic data. Both an ethanol−water extract of F. ancylantha and its phenolic constituents showed significant free-radical-scavenging and antimicrobial activities. No cytotoxicity, as evaluated by analysis of hypodiploid nuclei in HUVEC cells using propidium iodide staining, was observed for either the plant crude extract or its constituents

Pathway enrichment analysis: The pathways related to a <i>p</i>-value that excludes randomness and correlates with hypercholesterolaemia.

Pathway enrichment analysis: The pathways related to a p-value that excludes randomness and correlates with hypercholesterolaemia.</p

Metabolites discriminating hypercholesterolaemic from normocholesterolaemic samples, according to VIP score values.

Metabolites discriminating hypercholesterolaemic from normocholesterolaemic samples, according to VIP score values.</p

PCA score scatter plot (A) and PCA loading scatter plot (B) for the ¹H NMR data collected in 1D NOESY spectra acquired at 600 MHz.

Data are relative to 14 hypercholesterolaemic (green circles) and 16 normocholesterolaemic (red circles) human sera.</p

PLS-DA score scatter plot (A) and PLS-DA loading scatter plot (B) for the ¹H NMR data collected in 1D NOESY spectra acquired at 600 MHz.

Data represent 14 hypercholesterolaemic (green circles) and 16 normocholesterolaemic (red circles) human sera.</p

Graph of pathway impact and relative <i>p</i>-value.

Pathway analysis showing all matched pathways according to p-values from pathway enrichment analysis (y-axis) and pathway impact values from pathway topology analysis (x-axis). The colour and size of each circle are based on p-values and pathway impact values, respectively. Small p-values and large pathway impact circles indicate that the pathway is greatly perturbed. The top 5 pathways in order of p-values from the pathway analysis are numbered as follows: 1) pantothenate and CoA biosynthesis, 2) pyruvate metabolism, 3) glycolysis/ gluconeogenesis, 4) citrate cycle (TCA cycle) and 5) synthesis and degradation of ketone bodies.</p

Xanthohumol Induces Apoptosis in Human Malignant Glioblastoma Cells by Increasing Reactive Oxygen Species and Activating MAPK Pathways

The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-l-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme

Sesquiterpene Coumarins from <i>Ferula gumosa</i>

A new sesquiterpene coumarin, gumosin (1), two new sesquiterpene coumarin glycosides, gumosides A (2) and B (3), and 10 known compounds, namely, cauferoside (4), feselol (5), conferoside, ferilin, ferocaulidin, ligupersin A, conferol, and daucosterol, and the phenolic compounds acantrifoside E and 4-hydroxybenzoic acid 4-(6-O-sulfo)glucopyranoside, were isolated from a methanolic extract of Ferula gumosa roots. The structures of 1−3 were elucidated by spectroscopic data interpretation. The cytotoxic activity of the sesquiterpene coumarin derivatives was evaluated against a small panel of cancer cell lines

Supplementary Figure Legends from Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-EGFR Antibodies Converge on MEK/ERK Pathway Activation and Can Be Overcome by Combined MEK/EGFR Inhibition

PDF file - 116KB</p