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.