Inhibitory effects of flavonoids on HMG-CoA reductase and intestinal microflora growth

Abstract

The effects of flavonoids an inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is rate limiting enzyme in cholesterol biosynthesis, and growth-inhibition of intestinal microflora were investigated. Syrian hamster HMG-CoA reductase was overexpressed though the plasmid pKFT7-21 purified by Blue Sepharose CL-6B, chromatography. The IC50 values of 29 Flavonoids (flavones, flavanones, flavonols, flavanols, and isoflavones) were measured by modified microradio assay with [14C] HMG-CoA, and Vero cells were used to confirm cell proliferation. It was found that morin (2'', 3, 4'', 5, 7-pentahydroxyflavone) has remarkable effect on inhibition of HMG-CoA reductase having IC50 value of 16.7 (¡¾1.4) uM. It, however, did not show a significant morphological reversion of Vero cell at 100 mg/ml concentration. Regarding growth-inhibition of intestinal microflora, Bifidobacterium animalis, Enterococcus faecalis, Escherichia coli, and Clostridium perfringens were isolated with selective media and identified by 16S rRNA sequence homologue. Effects on growth-inhibition of intestinal harmful bacteria were determined by paper disks treated with one milligram flavonoids. Catechin and epicatechin showed a remarkable effect and morin was moderate for growth-inhibition against Cl. perfringens and E. coli, but did not show significant effect on useful bacteria. Comparing with total anaerobic intestinal bacteria at each morin concentration, relative composition of Bifidobacterium anmalis increased in and that of Cl. perfingens decreased.