Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare<sup>®</sup>)on the Contractile Response and on Pharmacologically Relevant Receptors in the Rat Bladder

Abstract

Hachi-mi-jio-gan extract (Harncare; HE), a galenical produced from the traditional Chinese herbal mixture Ba-Wei-Die-Huang-Wan, has been reported to improve lower urinary tract symptoms (LUTS) in patients. The present study was undertaken to clarify the pharmacological effects of HE on smooth muscle contraction and on pharmacologically relevant (muscarinic, 1,4-DHP and purinergic) receptors in the rat bladder. Additionally, the effects of repeated oral treatment with HE on the hepatic cytochrome P-450 (CYP) and on blood biochemical values in rats were examined. HE (10 mg/ml) inhibited significantly the acetylcholine-induced contraction of isolated rat bladder strips. The pD(2) value in the absence and presence of HE (10 mg/ml) was 5.14+/-0.16 and 3.99+/-0.17, respectively. HE (0.1 to 10 mg/ml) inhibited the specific binding of [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), (+)-[(3)H]PN 200-110 and alphabeta-methylene ATP [2,8-(3)H]tetrasodium salt ([(3)H]alphabeta-MeATP) in the rat bladder in a concentration-dependent manner. The respective IC(50) values were 6.85+/-0.94, 7.08+/-0.72 and 1.34+/-0.23 mg/ml. Based on IC(50) values, the binding activity of HE for purinergic receptors was shown to be significantly (about 7 times) greater than that for muscarinic and 1,4-DHP receptors. Repeated oral administration of HE (10, 30 and 100 mg/kg/day) for 4 weeks had little or no effect on the level and activity of hepatic CYP or on blood biochemical values in rats. In conclusion, the present study has shown that HE exerts significant binding activity for pharmacologically relevant receptors in the rat bladder and a relaxant effect on the acetylcholine-induced contraction of isolated muscle strips. HE seemed to exhibit little pharmacokinetic interaction with drugs.