Cytotoxic oleanane-type saponins from Albizia inundata.

Bioassay-guided fractionation of a CH(2)Cl(2)-MeOH extract of the aerial parts of Albizia inundata resulted in the isolation of two new natural oleanane-type triterpene saponins {3-O-[α-L-arabinopyranosyl(1→6)]-2-acetamido-2-deoxy-ß-D-glucopyranosyl oleanolic acid (1) and 3-O-[α-L-arabinopyranosyl(1→2)-α-L-arabinopyranosyl(1→6)]-2-acetamido-2-deoxy-ß-D-glucopyranosyl acacic acid lactone (2)} along with seven known saponins {3-O-[α-L-arabinopyranosyl(1→6)]-2-acetamido-2-deoxy-ß-D-glucopyranosyl echinocystic acid (3), 3-O-[ß-D-xylopyranosyl (l→2)-α-L-arabinopyranosyl(l→6)]-2-acetamido-2-deoxy-ß-D-glucopyranosyl acacic acid lactone (concinnoside D) (4), 3-O-[ß-D-glucopyranosyl(l→2)]-ß-D-glucopyranosyl oleanolic acid (5), 3-O-[α-L-arabinopyranosyl(1→2)-α-L-arabinopyranosyl(l→6)]-ß-D-glucopyranosyl oleanolic acid (6), 3-O-[ß-D-xylopyranosyl(1→2)-α-L-arabinopyranosyl(l→6)]-ß-D-glucopyranosyl oleanolic acid (7), 3-O-[α-L-arabinopyranosyl(l→2)-α-L-arabinopyranosyl(1→6)-[ß-D-glucopyranosyl(l→2)]-ß-D-glucopyranoside echinocystic acid (8), and 3-O-[ß-D-xylopyranosyl(l→2)-α-L-arabinopyranosyl(1→6)-[ß-D-glucopyranosyl(l→2)]-ß-D-glucopyranoside echinocystic acid (9)}. The structures of 1 and 2 were established on the basis of extensive 2D NMR ((1)H-(1)H COSY or DQF-COSY, HSQC, HMBC, TOCSY, and HSQC-TOCSY) spectroscopic, ESIMS, and chemical methods. Saponins 1, 3, 6, and 7 showed cytotoxicity against human head and neck squamous cells (JMAR, MDA1986) and melanoma cells (B16F10, SKMEL28) with IC(50) values in the range 1.8-12.4 µM, using the MTS assay.

Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma.

As part of a program to discover drug leads from plant biodiversity, the present investigation was undertaken to explore the anticancer potential of compounds derived from selected Latin American plants. Bioassay-guided fractionation of a crude extract of the aerial parts of Vassobia breviflora led to the isolation of the withanolide-type steroidal lactone withaferin A (1). This compound was tested for antiproliferative activity against the head and neck squamous cell carcinoma (HNSCC) cell lines, MDA1986, JMAR, UM-SCC-2, and JHU011. The inhibitory concentrations to reduce cell viability to 50% (IC(50)) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC(50) values in the range 0.5-2.2 µM. A mechanistic study showed that 1 induces apoptosis and cell death in HNSCC cells as well as a cell-cycle shift from G(0)/G(1) to G(2)/M. Cells treated with 1 exhibited inactivation of Akt and a reduction in total Akt concentration. This investigation constitutes the first report of the antiproliferative activity of withaferin A (1) against head and neck squamous carcinoma.

Concurrent EEG/fMRI analysis by multiway Partial Least Squares.

Data may now be recorded concurrently from EEG and functional MRI, using the Simultaneous Imaging for Tomographic Electrophysiology (SITE) method. As yet, there is no established means to integrate the analysis of the combined data set. Recognizing that the hemodynamically convolved time-varying EEG spectrum, S, is intrinsically multidimensional in space, frequency, and time motivated us to use multiway Partial Least-Squares (N-PLS) analysis to decompose EEG (independent variable) and fMRI (dependent variable) data uniquely as a sum of "atoms". Each EEG atom is the outer product of spatial, spectral, and temporal signatures and each fMRI atom the product of spatial and temporal signatures. The decomposition was constrained to maximize the covariance between corresponding temporal signatures of the EEG and fMRI. On all data sets, three components whose spectral peaks were in the theta, alpha, and gamma bands appeared; only the alpha atom had a significant temporal correlation with the fMRI signal. The spatial distribution of the alpha-band atom included parieto-occipital cortex, thalamus, and insula, and corresponded closely to that reported by Goldman et al. [NeuroReport 13(18) (2002) 2487] using a more conventional analysis. The source reconstruction from EEG spatial signature showed only the parieto-occipital sources. We interpret these results to indicate that some electrical sources may be intrinsically invisible to scalp EEG, yet may be revealed through conjoint analysis of EEG and fMRI data. These results may also expose brain regions that participate in the control of brain rhythms but may not themselves be generators. As of yet, no single neuroimaging method offers the optimal combination of spatial and temporal resolution; fusing fMRI and EEG meaningfully extends the spatio-temporal resolution and sensitivity of each method.