XXXX -dependent adjuvant activity of Kakkon-to extract exists in the high molecular weight polysaccharide fraction.

@entity630 @entity39 @entity19 @entity5 @entity635 @entity60 @entity1735 @entity5001 @entity683 @entity777 @entity1990 @entity637 @entity166
Kakkon-to, a traditional herbal medicine (Kampo formula), has been used historically in China and Japan for the treatment of @entity166 such as @entity683 and the common cold. However, the biological mechanism of its therapeutic action has not yet been elucidated. In this study, we investigated the immunological function of Kakkon-to and found that the high molecular weight fraction of the extract activated macrophages in vitro. This fraction was found to be composed primarily of @entity1735 and in vitro intensively stimulated @entity19 peritoneal macrophages that produce @entity630 inflammatory cytokines such as @entity5 @entity39 factor a ( @entity637 ), @entity635 ( @entity635 ), @entity60 ( @entity60 ), and @entity777 ( @entity777 ). The fraction did not activate macrophages from C3H/HeJ lacking @entity1990 ( @entity1990 ) or @entity5001 -deficient @entity19 , indicating that macrophage activation by the fraction was mediated by @entity1990 . The route of administration of the fraction into @entity19 regulated the kinetics of @entity637 production in immune organs. Intravenous administration induced @entity637 production in the four target organs of spleen, liver, lung, and Peyer  s patch; however, the most abundant production occurred in the liver and peaked at 30-60 min post administration. Peritoneal administration induced similar kinetics but the most abundant production occurred in the spleen. In contrast, oral administration induced @entity637 production in the liver, lung, and Peyer  s patch, but not in the spleen. Although liver and lung are @entity637 -abundant organs, production peaks in these organs occurred later than in Peyer  s patch. We also found that the fraction induced antibody production as an adjuvant against a specific antigen ovalbumin (OVA) when administered simultaneously and subcutaneously in a dose-dependent manner. Interestingly, the fraction induced IgG-class antibody in response to low doses of the antigen, which induced only IgM-class antibody when administered alone, suggesting that the fraction induces a class switch of immunoglobulin as an adjuvant in vivo. The high molecular weight fraction of Kakkon-to extract could be applicable as a potent immunostimulating drug and adjuvant.
