Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.
We investigated the protective effects of the traditional Japanese herbal medicine Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang in Chinese) (SRBT) against hypercholesterolemia and atherosclerotic lesions. We focused on atherosclerosis using female heterozygous Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. The total plasma cholesterol levels increased for up to 12 weeks after beginning a diet containing 0.1% cholesterol and then reached a plateau of about 600 mg dl(-1). When SRBT was administered at a dose of 1.0 g kg(-1)per day for 24 weeks, total plasma cholesterol levels were significantly decreased after 20-24 weeks. On the other hand, pravastatin at a dose of 10 mg kg(-1)per day produced a significant decrease in total plasma cholesterol levels from 4 to 24 weeks (about 105-130 mg dl(-1)). Moreover, 1.0 g kg(-1)per day of SRBT significantly decreased plasma low density lipoprotein (LDL) cholesterol levels but did not change either very low density lipoprotein (VLDL), or high density lipoprotein (HDL) cholesterol levels. Animals that received pravastatin had significantly decreased LDL cholesterol levels and VLDL cholesterol levels after 8 weeks and at 24 weeks. We also examined the expression of apoB, E and LDL receptor mRNA levels in the liver at 24 weeks after beginning the administration of 1.0 g kg(-1)per day of SRBT. Both apoE and LDL receptor mRNA levels were significantly increased compared with those in rabbits receiving the 0.1% cholesterol diet. SRBT at a dose of 1.0 g kg(-1)per day significantly depressed the intimal surface area of the thoracic aortae involved with atheromatous plaques. The present results suggest that SRBT may protect against hypercholesterolemia and atheromatous lesions by affecting apoE and LDL receptor mRNA gene expression in the liver.
Yoshie
F
F
Kampo & Pharmacognosy Laboratory, Tsumura & Co., Yoshiwara, Inashiki-gun, Ibaraki, 3586 Ami-machi, 300-1192 Japan. yoshii@pop02.odn.ne.jp
Iizuka
A
A
Kubo
M
M
Komatsu
Y
Y
Matsumoto
A
A
Itakura
H
H
Takeda
H
H
Matsumiya
T
T
Kondo
K
K
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000096:biosynthesis; D001057:Apolipoproteins E / Q000096:biosynthesis; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D004365:Drugs, Chinese Herbal; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; C095444:saiko-ka-ryukotsu-borei-to; D017035:Pravastatin