Combination Effects of Herbs in a Multi-herbal Formula: Expression of Juzen-taiho-to's Immuno-modulatory Activity on the Intestinal Immune System

Herbal formulas of traditional Japanese (Kampo), Chinese and Korean medicines usually comprise multiple herbs in a single formula. These medicines are expected to show their clinical effects by chemical, pharmacological and pharmaceutical combination effects of multi-herbs. However, little effort has been made so far to scientifically clarify the nature of such combination effects. Interestingly, for example, though a Kampo medicine Juzen-taiho-to (Shi-Quan-Da-Bu-Tang in Chinese) stimulates the immune functions of Peyer's patch cells, none of its single component herbs shows such activity. We thus examined the combination effect of herbs in the Juzen-taiho-to formula for the expression of its immuno-stimulating activity. Juzen-taiho-to, a composite formula of 10 herbs, has been generally considered to comprise two kinds of basic formula, each of which consists of four different herbs in addition to two others. The combinations of herbs based on these two basic formulas were evaluated for their stimulating activities on cytokine production from murine Peyer's patch cells both in vitro and ex vivo. Combined decoction of six among 10 herbs in Juzen-taiho-to is crucial for the expression of its stimulating activity on Peyer's patch cells. 3D-HPLC analysis of the ingredients in the fractions from the combined decoctions indicated that, in addition to quantitative changes of ingredients, alterations occur in their chemical composition by decoction of different herbs. The stimulating activity of Juzen-taiho-to on Peyer's patch cells results from the combination effect of its six essential component herbs. This combination effect is based on physicochemical interactions among the ingredients of the component herbs.