2004 Volume 21 Issue 1 Pages 34-38
In the treatment for the symptoms of Parkinson's disease, the catechol-O-methyl transferase (COMT) inhibitors are expected to mitigate side effects, such as wearing-off, which are caused by long-term administration of L-DOPA. It has been reported that Senkyu-chacho-san causes dopamine increase in a rat striatum. However, the detailed mechanism has not been clarified about the mechanism. Search for components inhibiting COMT led to the discovery of active compounds contained in Cnidii Rhizoma (Senkyu). The hot water extract from the Cnidii Rhizoma was subjected to distribution or gel filtration chromatography to give ferulic acid (1), sinapic acid (2), 5-hydroxy-ferulic acid (3), and chlorogenic acid (4). Their structures were determined by spectroscopic analyses, particularly by extensive 1D and 2D NMR studies. Isolation of 3 is the first report from Cnidii Rhizoma. These compounds can be regarded as substrate-mimetics, and the number of the hydroxyl group in benzene nucleus seems to have a significant effect on inhibitory activity against COMT. Compound 3 inhibited COMT in a competitive manner and its Ki value was calculated 43 μM from Lineweaber-Burk plots. These results suggest that the phenylpropanoides, which are the components of Cnidii Rhizoma, might raise the dopamine level in the brain.
