Pharmacological Modulation by Shakuyakukanzoto (Shao-Yao-Gan-Cao-Tang) and the Ingredients in Rat Intestinal Smooth Muscle

Shakuyakukanzoto (Shao-Yao-Gan-Cao-Tang), a formulation of Japanese herbal (Kampo) medicines, is composed of Paeoniae Radix and Glycyrrhizae Radix. Effects of Shakuyakukanzoto and the ingredients on rat intestinal tract were examined. Shakuyakukanzoto (0.01 0.3 mg/ml) relaxed a carbachol (CCh, 0.3 μM) -induced contraction in a concentration-dependent manner. Both components (Paeoniae Radix and Glycyrrhizae Radix) also relaxed the CCh-induced contraction. At 0.1 to 1 mM, their constituents (paeoniflorin and glycyrrhetic acid) and the metabolic products (18-αand 18-β-glycyrrhetinic acids) exerted almost the same actions. The relaxations induced by Shakuyakukanzoto were not modified by 1 μM nicardipine, 10 μM suramin (ATP receptor inhibitor) and several K channel inhibitors, but was attenuated by 20 μM IBMX (a phosphodiesterase inhibitor). Also, IBMX inhibited the relaxations induced by paeoniflorin and glycyrrhetic acid, but not by other ingredients. Nicardipine decreased the relaxation of just 18-α-glycyrrhetinic acid. Even in non-treatment with CCh, Shakuyakukanzoto relaxed the intestinal tract. CCh (0.3 μM) elicited spontaneous contractions in 23% specimens, depressed by application of Shakuyakukanzoto. These results indicate that Shakuyakukanzoto causes a remarkable relaxation by the anti-cholinergic and the PDE inhibitory actions, but by minor contribution of Ca channel inhibition. Thus, Shakuyakukanzoto exerts an anti-spasmodic action due to the interaction with pharmacological effects of its ingredients.