Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats.
Hypercholesterolemia is a dominant risk factor for the development and progression of atherosclerosis and cardiovascular diseases. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular diseases. Pueraria lobata is employed clinically to treat cardiovascular diseases in China. In the present study, the atheroscleroprotective potential of the herb's major active compound, puerarin, was investigated by monitoring serum lipid profile and major enzyme expressions on cholesterol homeostasis in Sprague-Dawley rats fed with control diet, hypercholesterolmic diet or hypercholesterolmic diet plus administration of puerarin (300 mg/kg/day, p.o.) for 4 weeks. Puerarin markedly attenuated the increased total cholesterol induced by hypercholesterolmic diet in both serum and liver. It caused a significant reduction in the atherogenic index. Expression of mRNA for hepatic 7alpha-hydroxylase (CYP7A1) was significantly enhanced but not for those of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and lanosterol 14alpha-demethylase (CYP51). To further explore the atheroscleroprotective potential of puerarin, acetylcholine induced endothelium-dependent vasorelaxation and endothelial nitric oxide synthase (eNOS) expression on isolated thoracic aortas were analyzed. Animals administered with puerarin suppressed the hypercholesterolemic diet induced impairment of eNOS expression, whereas there was no significant difference in the endothelium-dependent vasorelaxation among various groups of animals. These data indicated that puerarin reduced the atherogenic properties of dietary cholesterol in rats. Its hypocholesterolemic function may be due to the promotion of cholesterol and bile acids excretion in liver. Whether puerarin targets directly on cholesterol homeostasis or both cholesterol homeostasis and endothelial function remains to be determined.
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Li-Ping
LP
Yan
Shun-Wan
SW
Chan
Albert Sun-Chi
AS
Chan
Shi-Lin
SL
Chen
Xiao-Jun
XJ
Ma
Hong-Xi
HX
Xu
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000235:genetics; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007529:Isoflavones / Q000627:therapeutic use*; D008297:Male; D008516:Medicine, Chinese Traditional; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058886:Sterol 14-Demethylase; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002791:Cholesterol, Dietary; D007529:Isoflavones; D012333:RNA, Messenger; D014665:Vasodilator Agents; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D010088:Oxidoreductases; D006903:Hydroxymethylglutaryl CoA Reductases; D052250:Nitric Oxide Synthase Type III; D058886:Sterol 14-Demethylase; D002790:Cholesterol 7-alpha-Hydroxylase; D000109:Acetylcholine; C033607:puerarin