Natural polyphenol kaempferol and its epigenetic impact on histone deacetylases: Focus on human liver cells

Abstract

The flavonol kaempferol, which is found in many vegetables and fruits, is suggested to exhibit various and promising beneficial health effects in vitro and in vivo. Although there is strong evidence for health-promoting effects and good tolerability of kaempferol as common ingredient of daily nutrition, only little is known about the underlying pharmacodynamics and especially kaempferol-mediated effects on liver gene expression, enzyme levels, and phase I metabolism. Noteworthy, recent studies revealed that kaempferol is an interesting inhibitor of histone deacetylases with high affinity toward all members of HDAC families I, II, and IV that were tested. Therefore, the epigenetic activity of kaempferol could, at least in part, be responsible for the promising health effects and remain to be intensively studied in vivo. Investigation of hepatotoxic effects and interactions with CYP450 enzymes is one of the major prerequisites for a possible clinical use of kaempferol. Therefore, preclinical evaluation of high doses of kaempferol was performed with primary human hepatocytes, which are widely used as valuable tools to predict toxic drug effects on the human liver. Additionally, an in vivo chicken embryotoxicity assay to check for embryotoxic effects yielded good tolerability of kaempferol. According to the promising preliminary results, it would be important to evaluate long-term effects of low physiological doses of kaempferol compared to interventions with high pharmacological doses in future experiments.