Elsevier

Pharmacological Research

Volume 50, Issue 3, September 2004, Pages 223-230
Pharmacological Research

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

https://doi.org/10.1016/j.phrs.2004.02.003Get rights and content

Abstract

We investigated the antihypercholesterolemic effects of traditional Japanese herbal medicine Dai-saiko-to (Da-Chai-Hu-Tang in Chinese) in female heritable Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. The plasma total cholesterol levels increased for up to 12 weeks after beginning a diet containing 0.1% cholesterol then reached a plateau of about 603 mg dl−1. Dai-saiko-to was administered at doses of 0.5–1.0 g kg−1 per day or pravastatin 10 mg kg−1 per day for 24 weeks. Plasma total cholesterol levels were significantly decreased in the groups administered Dai-saiko-to 1.0 g kg−1 per day or pravastatin for 4–24 weeks, whereas there were no change with plasma phospholipid and triglyceride levels. However, Dai-saiko-to 1.0 g kg−1 per day significantly decreased plasma LDL cholesterol levels, but had no effect on either VLDL- or HDL-cholesterol levels.

Moreover, LDL-receptor mRNA levels in the liver were significantly increased in the Dai-saiko-to 1.0 g kg−1 per day group compared with those of animals receiving the 0.1% cholesterol diet. In addition, both groups receiving Dai-saiko-to 1.0 g kg−1 per day and pravastatin showed a significantly reduced percentage of intimal surface area of thoracic aorta involved with atheromatous plaques in the thoracic aorta at 24 weeks.

These results indicated that Dai-saiko-to 1.0 g kg−1 per day significantly decreased the plasma cholesterol levels and atheromatous plaque area due to expression of the LDL mRNA gene in the liver.

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

References (37)

  • Y Hanasaki et al.

    The correlation between active oxygens scavenging and antioxidative effects of flavonoids

    Free Radic. Biol. Med.

    (1994)
  • M.G.L Hertog et al.

    Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Eldery Study

    Lancet

    (1993)
  • Multiple risk factor intervention trial research group. Multiple risk factor intervention trial, risk factor changes...
  • T Kurosawa et al.

    New mutant rabbit strain with hypercholesterolemia and atherosclerotic lesion produced by serial inbreeding

    Lab. Anim. Sci.

    (1995)
  • S Yamano et al.

    Effects of Dai-saiko-to on lipid metabolism and common carotid hemodynamics in patients with hyperlipidemia

    J. Tradit. Med.

    (1994)
  • F Yoshie et al.

    Antiatherosclerotic effect of Dai-saiko-to in the Kurosawa and Kusanagi hypercholesterolemic rabbit

    Res Commun Pharmacol Toxicol

    (2000)
  • L.L Wu et al.

    A rapid Micro-scale procedure for determination of the total lipid profile

    Clin. Chem.

    (1989)
  • J.M Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • Cited by (0)

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