2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera.

Preparations of the roots of the medicinal plant Withania somnifera (L.) Dunal commonly called ashwagandha have been used for millennia in the Ayurvedic medical tradition of India as a general tonic to relieve stress and enhance health, especially in the elderly. In modern times, ashwagandha has been shown to possess intriguing antiangiogenic and anticancer activity, largely attributable to the presence of the steroidal lactone withaferin A as the major constituent. When cultured using the aeroponic technique, however, this plant was found to produce a new natural product, 2,3-dihydrowithaferin A-3beta-O-sulfate (1), as the predominant constituent of methanolic extracts prepared from aerial tissues. The characteristic bioactivities exhibited by 1 including inhibition of cancer cell proliferation/survival, disruption of cytoskeletal organization and induction of the cellular heat-shock response paralleled those displayed by withaferin A (2). The delayed onset of action and reduced potency of 1 in cell culture along with previous observations demonstrating the requirement of the 2(3)-double bond in withanolides for bioactivity suggested that 1 might be converted to 2 in cell culture media and this was confirmed by HPLC analysis. The abundant yield of 1 from aeroponically cultivated plants, its good aqueous solubility and spontaneous conversion to 2 under cell culture conditions, suggest that 1 could prove useful as a readily formulated prodrug of withaferin A that merits further evaluation in animal models.

Sorbifolivaltrates A-D, diene valepotriates from Valeriana sorbifolia(1).

Four new diene valepotriates, sorbifolivaltrates A-D ( 1- 4), and the known compounds isovaltrate ( 5), valtrate ( 6), seneciovaltrate ( 7), valtrate hydrine B3 ( 8), and valtrate hydrine B7 ( 9), have been isolated by bioassay-guided fractionation of the cytotoxic hexanes and methyl ethyl ketone crude extracts of the aerial parts of Valeriana sorbifolia occurring in the Sonoran desert. The structures of 1- 4 were determined on the basis of their high-resolution mass spectrometric and NMR spectroscopic data. All compounds exhibited weak to moderate cytotoxicity against the human metastatic prostate cancer cell line, PC-3M.

Zinagrandinolides A-C, cytotoxic delta-elemanolide-type sesquiterpene lactones from Zinnia grandiflora.

Three new delta-elemanolide-type sesquiterpene lactones, zinagrandinolides A-C (1-3), and the known delta-elemanolide 4 have been isolated by a bioassay-guided fractionation of a cytotoxic hexane extract of the aerial parts of Zinnia grandiflora. The structures of 1-3 were determined on the basis of high-resolution mass and NMR data. All compounds exhibited strong cytotoxicity against the cancer cell lines NCI-H460, MCF-7, SF-268, and MIA Pa Ca-2 and the normal human fibroblast cell type WI-38, but none showed significant selectivity.

Metabolic profiling and phylogenetic analysis of medicinal Zingiber species: Tools for authentication of ginger (Zingiber officinale Rosc).

Phylogenetic analysis and metabolic profiling were used to investigate the diversity of plant material within the ginger species and between ginger and closely related species in the genus Zingiber (Zingiberaceae). In addition, anti-inflammatory data were obtained for the investigated species. Phylogenetic analysis demonstrated that all Zingiber officinale samples from different geographical origins were genetically indistinguishable. In contrast, other Zingiber species were significantly divergent, allowing all species to be clearly distinguished using this analysis. In the metabolic profiling analysis, the Z. officinale samples derived from different origins showed no qualitative differences in major volatile compounds, although they did show some significant quantitative differences in non-volatile composition, particularly regarding the content of [6]-, [8]-, and [10]-gingerols, the most active anti-inflammatory components in this species. The differences in gingerol content were verified by HPLC. The metabolic profiles of other Zingiber species were very different, both qualitatively and quantitatively, when compared to Z. officinale and to each other. Comparative DNA sequence/chemotaxonomic phylogenetic trees showed that the chemical characters of the investigated species were able to generate essentially the same phylogenetic relationships as the DNA sequences. This supports the contention that chemical characters can be used effectively to identify relationships between plant species. Anti-inflammatory in vitro assays to evaluate the ability of all extracts from the Zingiber species examined to inhibit LPS-induced PGE(2) and TNF-alpha production suggested that bioactivity may not be easily predicted by either phylogenetic analysis or gross metabolic profiling. Therefore, identification and quantification of the actual bioactive compounds are required to guarantee the bioactivity of a particular Zingiber sample even after performing authentication by molecular and/or chemical markers.

PHOTOSYNTHETIC PATHWAYS OF HESPERALOE FUNIFERA AND H. NOCTURNA (AGAYACEAE): NOVEL SOURCES OF SPECIALTY FIBERS.

Hesperaloe funifera and H. nocturna are currently being studied as potential new sources of fibers for specialty papers. This study investigated canopy architecture and light interception in H. funifera, and gas exchange in both species. H. funifera is an acaulescent rosette species with stiff, upright leaves. Mean leaf angle for 3-year-old plants was 70° from horizontal, and more than 90% of the leaf surface was at angles greater than 50°. Vertical orientation of leaves reduced seasonal variation in light interception and midday light interception during summer months. High leaf angles are interpreted as an adaptation to arid habitats that could reduce this species' suitability for cultivation in more humid areas. Both H. funifera and H. nocturna had leaf-tissue water contents and mesophyll-succulence values intermediate between previously investigated Agavaceae known to be either C3 or Crassulacean acid metabolism (CAM) plants. Both species proved to have CAM, however. Gas exchange characteristics varied with leaf age, with older leaves having higher assimilation rates, greater water-use efficiency, and a higher proportion of nighttime CO2 uptake. Interestingly, these older leaves had mesophyll succulence values closer to those of typical C3 species. These Hesperaloe species can thus be characterized as nonsucculent CAM plants. Both species showed CO2 uptake rates of 5-8 µmol m-2 sec-1 expressed on a total-surface-area basis and 10-18 µmol m-2 sec-1 expressed on a projected-leaf-area basis. Expanded cultivation of species possessing CAM in marginal areas has been recommended recently; the physiological studies reported here along with previous studies of their economic botany identify these Hesperaloe species as good crop candidates for dry regions.