Abstract Title:

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

Abstract Source:

Phytother Res. 2011 Mar ;25(3):424-8. Epub 2010 Aug 23. PMID: 20734327

Abstract Author(s):

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

Article Affiliation:

Ku-Aida Tuansulong

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 (K(i)) 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 HMG-CoA with K(i) of 83.58 ± 4.37 µm and 83.59 ± 0.94 µm, respectively, and were also non-competitive with NADPH (K(i) 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.

Study Type : In Vitro Study

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