Morelloflavone from Garcinia dulcis as a novel biflavonoid inhibitor of HMG-CoA reductase

Ku Aida Tuansulong, Nongporn Hutadilok-Towatana, Wilawan Mahabusarakam, Decha Pinkaew, Kenichi Fujise

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Morelloflavone, a biflavonoid from Garcinia dulcis previously shown to have hypocholesterolemic activity, was examined for its effect on HMG-CoA reductase, the rate-limiting enzyme of the cholesterol biosynthetic pathway. By using the catalytic domain of house mouse HMG-CoA reductase, morelloflavone was found to inhibit the enzyme activity by competing with HMG-CoA whereas it was non-competitive towards NADPH. The inhibition constants (Ki) with respect to HMG-CoA and NADPH were 80.87 ± 0.06 μM and 103 ± 0.07 μM, respectively. Both flavonoid subunits of this compound, naringenin and luteolin, equally competed with HMGCoA with Ki of 83.58 ± 4.37 mM and 83.59 ± 0.94 μM, respectively, and were also non-competitive with NADPH (Ki of 182 ± 0.67 μM and 188 ± 0.14 μM, respectively). Due to these findings, we suggest that each subunit of morelloflavone would occupy the active site of the enzyme, thereby blocking access of its substrate. The present study thus demonstrates the ability of morelloflavone from G. dulcis to inhibit HMG-CoA reductase in vitro. As a result, this biflavonoid might serve as a new candidate for the future development of hypocholesterolemic agents.

Original languageEnglish (US)
Pages (from-to)424-428
Number of pages5
JournalPhytotherapy Research
Volume25
Issue number3
DOIs
StatePublished - Mar 2011

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Keywords

  • Biflavonoid
  • Cholesterol biosynthesis
  • Garcinia dulcis
  • HMG-CoA reductase inhibitor
  • Morelloflavone

ASJC Scopus subject areas

  • Pharmacology

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