Many investigations have indicated that elevated serum cholesterol levels may modify the biochemical properties of blood components and arterial intima, thus enhancing the progression of atherosclerosis.1-3) Atherosclerosis brings about cerebrovascular disease and coronary artery disease. The cholesterol-fed rabbit is an animal model for hypercholesterolemia and atheromatous formation. Formerly, we clarified that Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) prevents the development of atheromatous plaque formation in the aorta of cholesterol-fed rabbits by its antioxidative effect. 4) Vitamin E is a lipid-soluble antioxidant that inhibits lipid peroxidation and attenuates atherosclerosis. However, other studies showed that vitamin E might be a pro-oxidant.
5-7)Oren-gedoku-to (OGT, Huanlian-jie-du-tang in Chinese) is a Kampo formulation consisting of four medicinal plants (Table 1). It has been used for the treatment of cerebrovascular disease, hypertension, gastritis and liver disease in Japan. Several studies have shown that OGT scavenges superoxide anions and hydroxyl radicals in vitro. 8,9) Furthermore, it has been revealed that ingestion of OGT strengthens the protection of RBC membrane in oxidative stress, and improves protein and lipid metabolisms in human. 10,11) In this study, we investigated whether OGT is able to inhibit the progression of atheromatous formation in cholesterol-fed rabbits. Moreover, we compared the effect of OGT with those of KBG and vitamin E.
MATERIALS AND METHODS
Reagents. Medicines OGT (TJ-15) and KBG (TJ-25)were kindly provided by Tsumura & Co. Powdered extract of OGT was obtained from 4 kinds of medicinal plants mixed at the ratios shown in Table 1, and that of KBG was from 5 medicinal plants (Table 2). These nine medicinal plants are registered in the Japanese Pharmacopoeia.Animals Male Japanese white rabbits weighing 2 kg were purchased from Sankyo Laboratories (Toyama, Japan). Twenty-four rabbits were randomly divided into four groups. Medicine, Oriental Medical Center, Iizuka Hospital; Iizuka, Japan: c Department of Kampo Diagnostics, Institute of Wakan-yaku, Toyama Medical and Pharmaceutical University; Sugitani 2630, Toyama 930-0194, Japan: and d 21st Century COE Program, Toyama Medical and Pharmaceutical University; Sugitani 2630, Toyama 930-0194, Japan. Received September 9, 2004 accepted November 12, 2004; published online November 18, 2004 In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol an...