NAGUMO Seiji Hoshi University, Fac. Pharm. Sci., Lecturer, 薬学部, 講師 (80097162)
NOGUCHI Mariko Hoshi University, Fac. Pharm. Sci., Research Associate, 薬学部, 助手 (80247121)
KAMATA Katsuo Hoshi University Inst. Medicinal Chem., Associate Prof., 医薬品化学研究所, 助教授 (40121496)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Tanjin and takuran originate from Labiatae plants, and have been used as crude drugs promoting blood circulation (ku-oketsu) in Chinese medicine. We searched thetwo drugs for vasodilating components to rat aortic strips with endothelium.
(1) Tanjin, dried root of Salvia miltiorrhiza, contains lithospermic acids (LSA and LSA-B) as its chemical constituents. We reported that LSA-B is an endothelium-dependent vasodilator and that it induces hypotensive effects in rats through endothelium-dependent vasodilation of a resistance artery such as a mesenteric arterial bed.
In our continuing research for active ingredients of tanjin, the presenceof another effective vasodilator was presumed, which seemed to be an unknown component of this crude drug. On the basis of chemical and spectral results obtained during the period of this grant-in aid, the effective vasodilator was identified as (2S, 3S)-4-[(E)-2carboxy-ethenyl]-2-(3,4-dihydroxyphenyl)-2, 3-dihydro-7-hydroxy-3-benzofurancarboxylic acid (de
PL-LSA=8-epiblechnic acid), and was chemically derived from LSA and LSA-B by alkaline hydrolysis. In addition, dePL-LSA caused a sustained, slowly developing relaxation of rat aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium at a concentration 10^<-7>M.Taking into consideration the results of other four kinds of pharmacological experiments, we presume that dePL-LSA inhibits NE-induced contraction of the aortic strips through reduction in Ca^<2+> mobilization. DePL-LSA may be useful in the tretmanet of hypertension, because this agent inhibits NE-induced, sustained contraction.
(2)Since commercially-available takuran mostly comes from upper-ground part of Eupatorium fortunei (Compositae), we cultivated Lycopus lucidus in 1994 to get a harvest enough to investigate its vasodilating components. Through the chemical and chromatographic separation of a water-extract from the plant material, three compounds were isolated, which showed vasodilating activities. Any of them seemed to be an endothelium-independent vasodilator. Identification, efficiency and mechanism of them should further be investigated. Less