TY - JOUR
T1 - Morelloflavone from Garcinia dulcis as a novel biflavonoid inhibitor of HMG-CoA reductase
AU - Tuansulong, Ku Aida
AU - Hutadilok-Towatana, Nongporn
AU - Mahabusarakam, Wilawan
AU - Pinkaew, Decha
AU - Fujise, Ken
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Biflavonoid
KW - Cholesterol biosynthesis
KW - Garcinia dulcis
KW - HMG-CoA reductase inhibitor
KW - Morelloflavone
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U2 - 10.1002/ptr.3286
DO - 10.1002/ptr.3286
M3 - Article
C2 - 20734327
AN - SCOPUS:79952217473
SN - 0951-418X
VL - 25
SP - 424
EP - 428
JO - Phytotherapy Research
JF - Phytotherapy Research
IS - 3
ER -