Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice

Mi Ja Chung, Nak Ju Sung, Cheon Seok Park, Dong Keon Kweon, Alberto Mantovani, Tae Wha Moon, Sung-Joon Lee, Kwan Hwa Park

Research output: Contribution to journalArticle

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Abstract

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 7α-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.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalEuropean Journal of Pharmacology
Volume578
Issue number2-3
DOIs
Publication statusPublished - 2008 Jan 14

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Hep G2 Cells
Glycosides
Water
Cholesterol
Isoflavones
Antioxidants
LDL Receptors
Liver
LDL Lipoproteins
puerarin
Pueraria
Cholesterol 7-alpha-Hydroxylase
Messenger RNA
Inbred C57BL Mouse
Hydroxyl Radical
Solubility
Biological Availability
Superoxide Dismutase
Oxidoreductases
Gene Expression

Keywords

  • Antioxidant
  • HMG-CoA reductase
  • Low-density lipoprotein receptor
  • Puerarin glycoside

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice. / Chung, Mi Ja; Sung, Nak Ju; Park, Cheon Seok; Kweon, Dong Keon; Mantovani, Alberto; Moon, Tae Wha; Lee, Sung-Joon; Park, Kwan Hwa.

In: European Journal of Pharmacology, Vol. 578, No. 2-3, 14.01.2008, p. 159-170.

Research output: Contribution to journalArticle

Chung, Mi Ja ; Sung, Nak Ju ; Park, Cheon Seok ; Kweon, Dong Keon ; Mantovani, Alberto ; Moon, Tae Wha ; Lee, Sung-Joon ; Park, Kwan Hwa. / Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice. In: European Journal of Pharmacology. 2008 ; Vol. 578, No. 2-3. pp. 159-170.
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