Variable influence of kaempferol and myricetin on in vitro hepatocellular cholesterol biosynthesis

Flavonoids, e. g., quercetin, luteolin, and taxifolin, are known to inhibit hepatocellular cholesterol biosynthesis. Surprisingly, we found that some flavonoids, namely kaempferol and myricetin, are able to considerably stimulate cholesterol biosynthesis, particularly within a low concentration range (between 0.1 and 10 microM), while they show a variable degree of inhibition at higher concentrations. Kaempferol 3-glucoside even stimulated cholesterol synthesis up to 100 microM. In contrast, kaempferol 7-neohesperidoside was ineffective. These effects were more pronounced in rat hepatocytes than in HepG2 cells except for myricetin which acted stimulatory even at high concentrations in HepG2 cells. These opposing effects on cholesterol biosynthesis are exerted in an indirect manner and seem possible though differential modulation of the complex regulation of HMGCoA reductase.