In search of novel immune-modulatory compounds from British Columbia wild mushrooms and their effectiveness in inflammatory micro-circulation of mice

Natural products have been an integral component of people's health and health outcomes for thousands of years. In particular, several mushroom species have demonstrated beneficial therapeutic potential. The goals of this research are to explore the immune-stimulatory and anti-inflammatory potential of wild mushrooms native to the North Central region of British Columbia. Out of 42 mushroom extracts examined, four exhibited strong immune-stimulatory activity as assessed by induction of tumor-necrosis factor alpha (TNF-a) production in macrophage cells. Out of thirty-three extracts tests, nineteen demonstrated potent anti-inflammatory activity as determined by inhibition of lipopolysaccharide-induced TNF-a production in macrophage cells. Sodium hydroxide extract of Echinodontium trinctorium exhibited potent anti-inflammatory activity and was selected for further study. A small molecular weight (~5-25 kDa) carbohydrate was successfully purified using sequential size-exclusion and ion-exchange chromatography. GC-MS analysis showed that the polysaccharide has glucose (89.7%) as the major back-bone monosaccharide, and also the presence of other monosaccharides such as mannose (3.1%), galactose (2.8%), fucose (2.4%), and xylose (2.0%). The study also revealed the presence of 1,3-linked glucose linkages. Both the semi-purified anti-inflammatory compound(s) from E. tinctorium and the methanol extract of Inonotus obliquus can ameliorate histamine-induced vasodilation in the 2A arterioles (gluteus maximus muscle) in mice. This is the first study to demonstrate the anti-inflammatory activity of purified compounds and extracts from mushroom in an animal microcirculation model using intravital microscopy

Additional file 5: Table S3. of Transcriptomic profiles of aging in naïve and memory CD4+ cells from mice

Cis-regulatory analysis of genes differentially expressed (FDR ≤0.1) during aging by oPOSSUM-3. Table shows transcription factor binding sites found to be enriched in +/− 10 kb regions flanking transcription start site of target genes (excluding coding regions). See Methods for explanation of Z-score and Fisher p-value. (PPTX 42 kb

Additional file 3: Table S1. of Transcriptomic profiles of aging in naïve and memory CD4+ cells from mice

DAVID results from expanded gene list (FDR ≤0.1). Lists of genes differentially expressed between young and old mice at FDR ≤0.1 in naïve and memory CD4+ T cells were used as input, with all expressed genes in naïve and memory cells used as background. Broad terms such as “signal” and “disulfide bond” were excluded. A FDR of 0.05 was used as a threshold for enriched terms. No terms were significantly enriched in down-regulated gene lists. (PPTX 40 kb

Study sample characteristics.

<p>Data shown as mean (standard deviation) unless otherwise indicated.</p

Regional association plots of rs10198628 in MESA ancestry populations.

<p>European, African (A), Chinese, and Hispanic ancestry population (B).</p

Results for rs10198628 across body composition and atherosclerosis traits in the Framingham Heart Study (n = 3,158) and the GIANT Consortium (n = 77,157 to 133,828) modeled per copy of the A allele.

*<p>Odds ratio presented for CARDIoGRAM.</p

Association of validated SNPs for BMI (from Speliotes et al, Nature Genetics 2010) [39].

<p>All CT traits presented with the same coded allele, and all are modeled relative to the previously-published BMI trait-increasing allele. Z-statistic indicates direction relative to the coded allele.</p

Association of SNPs from a Recently Published GWAS of Body Fat Distribution^* (Heid IM et al, NG, 2010) [32].

<p>All data modeled relative to the previously-published trait-increasing allele; the z-statistic indicates the effect direction relative to the coded allele.</p>*<p>Measured by WHR-adjusted-for-BMI.</p

Results of rs1659258 in the VATGen meta-analysis; results modeled per copy of the trait-increasing A allele and for independent validation in the GIANT Consortium (non-overlapping studies).^*

*<p>GIANT sample sizes for women and men are as follows: BMI (58208, 49092); WC (39471, 31406).</p

Study Sample Characteristics, VATGen Consortium.

<p>Data shown as mean (standard deviation) unless otherwise indicated.</p>*<p>cm3 for the Framingham Heart Study; all other studies are measured in cm2.</p