Melissa officinalis Extract Inhibits Herpes Simplex Virus-I Glycoprotein B Interaction with Heparin Sulfate

Herpes simplex virus 1, HSV1, is the primary cause of herpes labialis in humans. Drugslikeacycloviranditsderivativesareavailablefortreatment,butwithincreased use and the number of immune compromised patients, the development of resistance to these drugsisincreasing. Extracts of the botanical, Melissa officinalis, have previously been reported to contain antiviral activity toward HSV1. Our initial studies confirmed earlier results that constituents of Melissa officinalis interacted directly with the virus and inhibited HSV1 binding to cells during the initiation of infection. Further studies demonstrated that a component in Melissa officinalis bound specifically to the viral glycoprotein B. Virion structure was shown to be stable at low concentrations of Melissa officinalis, however at a ten-fold higher concentration than that which inhibited binding, virion structure was completely disrupted suggesting a second, virucidal, mode of inhibition. Melissa officinalis was shown to inhibit other alpha herpes viruses as well as having intermediate inhibitory activity against other viruses from the adenoviridae, poxviridae, papovaviridae, and rhabdoviridae families

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

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

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

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

Transcriptional profiling of M1/M2 macrophage polarization induced by <i>Astragalus membranaceus.</i>

<p>Human genes involved in defining M1/M2 polarization are shown <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012561#pone.0012561-Martinez1" target="_blank">[47]</a>. The transcriptional regulatory effect of each gene following treatment of PBMCs with <i>Astragalus</i> extract is indicated (‘Expression’ column), with positive values representing increased expression, and negative values representing repressed expression. The ‘X’ (in the ‘M1 like’ or M2 like' column) indicates that the change in gene expression (induced or repressed) following <i>Astragalus</i> treatment was similar to that previously observed following monocyte maturation to either an M1-like or M2-like macrophage polarization.</p

Temporal regulation of gene expression in PBMCs following <i>Astragalus membranaceus</i> treatment.

<p>PBMCs were treated with <i>Astragalus</i> extract for 3, 8 or 18 hours. 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 represents the roles and overall comparison of genes induced at 3, 8 and 18 hours post <i>Astragalus</i> treatment. Part C lists representative genes induced at 3, 8 and/or 18 hours post <i>Astragalus</i> treatment.</p