Antrodia cinnamomea Galactomannan Elicits Immuno-stimulatory Activity Through Toll-like Receptor 4

Antrodia cinnamomea (A. cinnamomea) is a medicinal fungus used in traditional Chinese medicine to treat different kinds of ailments, including liver diseases, abdominal pain, drug intoxication, diarrhea, itchy skin, hypertension, and cancer. Polysaccharides have been identified as one of the major pharmacologically active ingredients present in A. cinnamomea. The present study aims to investigate the immunoenhancing activity of galactomannan isolated from A. cinnamomea. The cold water-soluble polysaccharide (galactomannan-repeated; MW>70 kDa; named ACP) of A. cinnamomea was isolated, and immunostimulatory properties were studied through different immune cell models including mouse macrophages and human dendritic cells. Through Toll-like receptor 4, ACP stimulated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in J774A.1 mouse macrophages, mouse peritoneal macrophages and human dendritic cells. It was further identified that ACP elicited its immunostimulatory activity through protein kinase C-α (PKC-α) and mitogen activated protein kinases (MAPK) phosphorylation. Furthermore, ACP exerted the endotoxin tolerance-like effect through NF-κB inhibition. These findings demonstrate the potential of A. cinnamomea galactomannan as an immunostimulator or an adjuvant in immunotherapy and vaccination.