In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections

Regulation of Inflammatory Gene Expression in PBMCs by Immunostimulatory Botanicals

Many hundreds of botanicals are used in complementary and alternative medicine for therapeutic use as antimicrobials and immune stimulators. While there exists many centuries of anecdotal evidence and few clinical studies on the activity and efficacy of these botanicals, limited scientific evidence exists on the ability of these botanicals to modulate the immune and inflammatory responses. Using botanogenomics (or herbogenomics), this study provides novel insight into inflammatory genes which are induced in peripheral blood mononuclear cells following treatment with immunomodulatory botanical extracts. These results may suggest putative genes involved in the physiological responses thought to occur following administration of these botanical extracts. Using extracts from immunostimulatory herbs (Astragalus membranaceus, Sambucus cerulea, Andrographis paniculata) and an immunosuppressive herb (Urtica dioica), the data presented supports previous cytokine studies on these herbs as well as identifying additional genes which may be involved in immune cell activation and migration and various inflammatory responses, including wound healing, angiogenesis, and blood pressure modulation. Additionally, we report the presence of lipopolysaccharide in medicinally prepared extracts of these herbs which is theorized to be a natural and active component of the immunostimulatory herbal extracts. The data presented provides a more extensive picture on how these herbs may be mediating their biological effects on the immune and inflammatory responses

Dynamics of neutrophil aggregation

Neutrophil aggregation has been widely evaluated from changes in light transmission. Using direct particle counting, we demonstrated that light transmission does not accurately reflect aggregation, and showed that in contrast to previous reports, newborn neutrophils do not aggregate irreversibly. We developed a flow cytometric technique to measure the kinetics of neutrophil aggregation, including latent times for onset of aggregation, initial forward and reversal rates, and maximal extents of aggregation. The kinetics of neutrophil aggregation were related to changes in initial cell concentration, stir speed (shear), and activator type and concentration. Physiologic activators stimulated reversible aggregation, accompanied by an exponential decay in aggregatory potential with increasing time. The fraction of occupied activator receptors was found to correspond to the fraction of maximal rates or extent of aggregation. Monoclonal antibodies were used to show that neutrophil aggregation is mediated by the Mac-1 integrin (CD11b/CD18). Direct measurements of aggregation have enhanced our understanding of the (patho)physiologic process of neutrophil aggregation

Pentaspiranes and hexaspiranes with 1,3-dioxane or 1,3-oxathiane rings: synthesis and stereochemistry

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Endotoxin concentration present in botanical extracts.

<p>Endotoxin concentrations in the botanical extracts listed were measured using a modified Limulus Amebocyte Lysate assay. Concentrations (endotoxin units/ml; EU/ml) were determined by comparison to an <i>Escherichia coli</i> standard solution. For <i>Astragalus</i> and <i>Urtica</i>, multiple extract preparations were prepared at different times using multiple lots of plant material obtained from the supplier (Samples I–IV and Samples I–V, respectively).</p

Host gene expression regulated by <i>Astragalus membranaceus</i> treatment of PBMCs.

<p>Genes were sorted based on a threefold (<i>P</i><0.01) or greater level of induction for <i>Astragalus</i> treated PBMCs for 18 hours (Astra column). Only genes involved in the immune/inflammatory response are shown. Changes (n-fold) in expression level relative to those of ethanol-treated cells are shown within each box. Red boxes represent genes induced 100-fold or higher, orange boxes represent genes induced 10 to 100-fold, and yellow boxes represent genes induced 3 to 10-fold. Additional botanical treatments include <i>Sambucus cerulea</i> (Sambu column) and <i>Andrographis paniculata</i> (Andro column).</p

Scatter plot representation of botanical extract regulation of gene expression.

<p>Microarray analyzed gene data was plotted to compare gene expression differences between botanical and ethanol treatment of PBMCs (Part A). Each spot on the plots represents a specific gene. Only genes with present calls in both treatments are shown. The diagonal lines off the center represent 2-, 3-, 10-, and 30-fold levels of induction or repression of gene expression. Part B illustrates comparative analysis between different botanical treatments of PBMCs.</p