若干の和漢生薬，とくに赤しゃくエキスによるプラスミン及びトロンビンの阻害様式について

Abstract

Modern attempts to re-evaluate Chinese traditional herb medicine conducted in recent China are regarded to be very much promising and therefore of noteworthy. The present paper is to introduce the results by the authors that some Chinese herb extracts which have been believed traditionally to improve the circulation disturbance in patients, do show very characterisitc type of inhibition of plasmin or thrombin enzymatically. The author's first screening test of 12 kinds of the herbs demonstrated luckily that several herb extracts potently inhibited plasmin or thrombin with dose dependency. Among them, Chi-shao (a kind of Paeonia Radix) was found to be the strongest inhibitor of plasmin. Therefore, mode of inhibition by Chi-shao was studied by using synthetic chromogenic substrate in the presence or absence of synthetic inhibitors such as EACA or t-AMCHA, which led to the following conclusions.When the synthetic substrate are used to measure the enzyme activities, it is reasonably deduced that the plasmin-inhibition is the immediate and noncompetitive action, while the thrombin-inhibition, the slow and uncompetitive. When ca. 20mM of the synthetic inhibitor, AMCHA is present, inhibition of plasmin clearly reversed (disappeared). It is to be reminded that “mM order” concentration of AMCHA can inhibit active amidolytic activity while “ μM order” AMCHA can inhibit the fibrinolytic activity only indirectly through the binding of AMCHA to the “kringle part” of the plasmin molecule. Therefore the peculiar phenomena above mentioned may be well understood by assuming that the active ingredient of Chi-shao exerts two kinds of inhibition; one is towards the active center, while the other is towards the lysine binding site (LBS) of “kringle part” of plasmin. The similarity of the mode of action between Chi-shao inhibitor and α2 plasmin inhibitor is to be emphasized.