Effects of Dai-saiko-to (Da-Chai-Hu-Tang) on plasma lipids and atherosclerotic lesions in female heterozygous heritable Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits
Introduction
Hypercholesterolemia is one of the most important risk factors for coronary artery diseases and/or atherosclerosis. Previous trials have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor such as statin’s decreased plasma lipid concentrations and prevent coronary artery diseases [1], [2]. Therefore, reduction of plasma cholesterol levels is available for diminishing the progression of coronary artery diseases. A number of antihypercholesterolemic medicines are used to improve the plasma lipid levels. It is obvious that hyperlipidemia due to familial hypercholesterolemia (FH) has become an increasing risk factor for coronary heart disease and progression of the atherosclerotic lesions. The Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits, which lack a LDL-receptor gene, are FH models similar to the Watanabe heritable hyperlipidemic (WHHL) rabbit [3], [4].
Some traditional Japanese herbal medicines have been used clinically for hyperlipidemia, diabetes mellitus and obesity in Japan. Dai-saiko-to, one of these traditional Japanese herbal medicine, has been reported to have an antihyperlipidemic effect in patients with hypercholesterolemia [5], lowering hepatic triglyceride biosynthesis in HepG2 human hepatocyte cells [6], and experimental hypercholesterolemic models [7]. However, the pharmacological mechanisms of Dai-saiko-to have not yet been elucidated.
In this study, we investigated the pharmacological effects of Dai-saiko-to and pravastatin, as a control medicine, on the plasma lipid levels and antiprogression of atheromatous plaque area in female heritable heterozygous hypercholesterolemic rabbits. And, we were also able to identify the apolipoprotein-E, apolipoprotein-B, and LDL-receptor mRNA gene expression in the liver.
Section snippets
Drugs
Pravastatin sodium was purchased from Sankyo Co. (Tokyo, Japan), and Dai-saiko-to (Da-Chai-Hu-Tang in Chinese) (Lot: 230008010), manufactured by Tsumura & Co. (Tokyo, Japan). This formula is a dried decoction of a mixture of eight medicinal herbs. A total of 6 g of Bupleurum Root (Umbelliferae, Bupleurum falcatum Linné.), 4 g of Pinellia Tuber (Araceae, Pinellia ternata BRETT.), 3 g of Scutellaria Root (Labiatae, Scutellaria baicalensis GEORGI.), 3 g of Peony Root (Paeoniaceae, Paeonia lactiflora
Three-dimensional HPLC profile of Dai-saiko-to
The three-dimensional HPLC profile of the methanol solution of Dai-saiko-to is shown in Fig. 1. This formula is a dried decoction of a mixture of eight medicinal herbs (Table 1). The analysis based on UV-absorption clearly shows the presence of the following constituents in the Dai-saiko-to powder: saikosaponin b1 and saikosaponin b2 (originating from Bupleurum Root); wogonin, wogonin 7-O-glucronoside, oroxylin A, oroxylin A 7-O-glucoside, baicalin, baicalein 7-O-glucoside, and skullcapflavone
Discussion
We investigated the antihypercholesterolemic effects of the Japanese traditional herbal medicine Dai-saiko-to (Da-Chai-Hu-Tang) and pravastatin in female heritable (heterozygous) Kurosawa and Kusanagi-hypercholesterolemic rabbits (KHC rabbits). Dai-saiko-to, one of these traditional Japanese herbal medicine, has been reported to have an antihyperlipidemic effect in patients [5] with hypercholesterolemia and experimental hypercholesterolemic models [7], [14]. Generally, it is well known that
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