Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice.
Puerarin is an isoflavone derived from Kudzu roots and has antioxidant and hypocholesterolemic effects; however, its insolubility often limits its biological availability in vivo. Using a novel transglycosylation process, the solubility of puerarin glycosides was increased >100-fold, but it was not known whether these modified puerarin glycosides maintained biological activities. We found that water-soluble puerarin glycosides fully maintained antioxidant activities compared with puerarin assessed by radical scavenging activity, reducing power assay, superoxide dismutase activity, and non-site-specific hydroxyl radical scavenging activity. Both puerarin and its glycosides also significantly reduced low-density lipoprotein (LDL) oxidation. Mice fed with puerarin glycosides (0.1% w/w) showed significantly reduced plasma total cholesterol levels, thus, we further investigated their hypocholesterolemic mechanisms by assessing several key gene expressions both in vitro and in vivo. Puerarin and its glycosides induced multiple changes in hepatic cholesterol metabolism. The LDL receptor promoter activity was increased dose-dependently in puerarin glycosides-treated HepG2 cells. Accordingly, the expression of LDL receptor mRNA and protein were also significantly increased in HepG2 cells and mouse livers. The transcription and translation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase were down-regulated both in vitro and in vivo. The cholesterol 7alpha-hydroxylase (CYP7A1) mRNA levels were not affected in vitro but significantly up-regulated in the mouse livers. Collectively, our results show that puerarin and its glycosides are biologically fully active isoflavone and have antioxidant and hypocholesterolemic effects in HepG2 cells and in C57BL/6J mice. In the livers, hypocholesterolemic effects of puerarin glycoside may be achieved by multiple mechanisms including increasing LDL uptake, reducing cholesterol biosynthesis, and possibly enhancing cholesterol degradation.
Chung
Mi Ja
MJ
Division of Food Bioscience and Technology, College of Life Science and Biotechnology, Institute of Biomedical Sciences and Food Safety, Korea University, Seoul 136-713, South Korea.
Sung
Nak-Ju
NJ
Park
Cheon-Seok
CS
Kweon
Dong-Keon
DK
Mantovani
Alberto
A
Moon
Tae-Wha
TW
Lee
Sung-Joon
SJ
Park
Kwan-Hwa
KH
D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014867:Water / Q000737:chemistry
D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D006027:Glycosides; D007529:Isoflavones; D012333:RNA, Messenger; D011973:Receptors, LDL; D012997:Solvents; D014867:Water; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse; C033607:puerarin