THE
IN VITRO-INHIBITORY EFFECT OF FLAVONOID ASTILBIN ON 3 - HYDROXY - 3 - METHYLGLUTARYL COENZYME A REDUCTASE ON VERO
CELLS. P Chan, F-L Hsu* Department of Medicine,
Taipei Medical College and Wan-Fang Hospital; and School of Pharmacy, Taipei
Medical College, Taipei, Taiwan Coronary heart disease (CHD)
is still the leading cause of mortality in Western industrialised countries.
Epidemiological studies have shown that hypercholesterolemia is a major risk
factor for coronary heart disease. In fact, clinical trials in lipid lowering
therapy have revealed decrease of cardiac event and mortality.
3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitor has been
shown to decrease cardiac event and mortality.
So developing new inhibitors of cholesterol synthesis is still a major
issue in pharmaceutical sciences.
Flavonoids are polyphenolic natural antioxidants existed in vegetables, fruits
and beverages such as tea and wine. It has been shown to have clinical benefits
to reduce mortality of CHD. The methods for analysis of specific inhibitors of
mevalonate biosynthesis have already been well- establisbed by using Vero
cells, a cell line obtained from kidneys of African green monkey. Flavonoids
isolated from different traditional Chinese herbs were dissolved in 100% DMSO
and incubated with Vero cells with or without the addition of 1 mM mevalonate
or 5 mM sodium acetate for 24 h in order to observe cell growth. Incubation
with 1 Mm mevalonate into the cell culture medium could enhance cell growth whereas
addition of 5 mM sodium acetate had no effect. Pravastatin, a specific HMG-CoA
reductase inhibitor, was used as positive control which could inhibit Vero
cells growth effectively and cell growth inhibition was reversible after
incubation with 1 mM mevalonate. About 40 flavonoid compounds were used for
study, only two compounds: quecitrin and astilbin (belongs to flavonol group)
showed significant growth inhibition of Vero cells at the concentration of 100
mg/ml. This study shows that some flavonoid compounds isolated from traditional
medicinal herbs were effective HMG-CoA reductase inhibitors which might be
developed into new hypocholesterolemic agents.
