BACKGROUND: Epidemiological studies have shown that hypercholesterolemia is a major risk factor for coronary heart disease. In clinical trials of lipid lowering therapy, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitor has been shown to decrease cardiac events and mortality. Flavonoids are polyphenolic natural antioxidants existing in vegetables, fruits and beverages such as tea and wine. Previous studies have shown that some antioxidants had hypocholesterolemic effect, and flavonoid intake was associated with the decrease of mortality from coronary artery disease. The aim of this study was to evaluate the inhibitory effect of flavonoids on HMG-CoA reductase. METHODS: The methods for analysis of specific inhibitors of mevalonate biosynthesis have been well-established, using Vero cells, a cell line obtained from kidneys of African green monkeys. Flavonoids isolated from different traditional Chinese herbs were dissolved in DMSO and incubated with Vero cells with or without the addition of 1 mM mevalonate or 5 mM sodium acetate in order to observe cell growth for 24 h. RESULTS: Concentrations of 1 mM mevalonate or 5 mM sodium acetate were added into culture medium in order to observe the effect on cell growth. Different concentrations of pravastatin to inhibit cell growth were used as a positive control. About 40 flavonoid compounds were used for study, only one compound, astilbin (belonging to the flavonol group), showed significant inhibition of Vero cell growth. CONCLUSIONS: This study shows that one flavonoid compound, isolated from traditional medicinal herbs, may be an effective HMG-CoA reductase inhibitor which might be developed into a new hypocholesterolemic agent.
BACKGROUND: Epidemiological studies have shown that hypercholesterolemia is a major risk factor for coronary heart disease. In clinical trials of lipid lowering therapy, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitor has been shown to decrease cardiac events and mortality. Flavonoids are polyphenolic natural antioxidants existing in vegetables, fruits and beverages such as tea and wine. Previous studies have shown that some antioxidants had hypocholesterolemic effect, and flavonoid intake was associated with the decrease of mortality from coronary artery disease. The aim of this study was to evaluate the inhibitory effect of flavonoids on HMG-CoA reductase. METHODS: The methods for analysis of specific inhibitors of mevalonate biosynthesis have been well-established, using Vero cells, a cell line obtained from kidneys of African green monkeys. Flavonoids isolated from different traditional Chinese herbs were dissolved in DMSO and incubated with Vero cells with or without the addition of 1 mM mevalonate or 5 mM sodium acetate in order to observe cell growth for 24 h. RESULTS: Concentrations of 1 mM mevalonate or 5 mM sodium acetate were added into culture medium in order to observe the effect on cell growth. Different concentrations of pravastatin to inhibit cell growth were used as a positive control. About 40 flavonoid compounds were used for study, only one compound, astilbin (belonging to the flavonol group), showed significant inhibition of Vero cell growth. CONCLUSIONS: This study shows that one flavonoid compound, isolated from traditional medicinal herbs, may be an effective HMG-CoA reductase inhibitor which might be developed into a new hypocholesterolemic agent.