Dioscorea (Dioscoreae rhizoma), cornus (Corni fructus), alisma (Rhizoma alismatis), holelen (Poria), rehmannia (Rehmanniae radix) and tree peony bark (Moutan radicis cortex)

Die-Huang-Wan is a mixture of six herbs used to lower plasma glucose by increasing insulin  secretion in normal rats. Die-Huang-Wan contains the herbs dioscorea (Dioscoreae rhizoma), cornus (Corni fructus), alisma (Rhizoma alismatis), holelen (Poria), rehmannia (Rehmanniae radix) and tree peony bark (Moutan radicis cortex). The present study was designed to clarify the major herb contributing to the plasma glucose-lowering action of Die-Huang-Wan in rats. A decrease in plasma glucose was not observed in Wistar rats treated with the cornus-deleted formula of Die-Huang-Wan; however, the action was retained in the other herb-deleted formulas containing cornus. In normal rats, the decrease in plasma glucose and increase in plasma insulin concentrations were dependent on the dose of cornus and were similar to those produced by Die-Huang-Wan. Treatment of Wistar rats with each of the other five herbs separately did not result in a decrease in plasma glucose. Moreover, the increase in plasma insulin or reduction in plasma glucose resulting from cornus treatment was blocked by atropine or 4-diphenylacetoxy-N-methylpiperidine methiodide mustard, indicating mediation of muscarinic M(3) receptors similar to that caused by Die-Huang-Wan. These results suggest that cornus is the major contributor to the plasma glucose-lowering action in Die-Huang-Wan in normal rats.