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Natural Polyphenol Kaempferol and Its Epigenetic Impact on Histone Deacetylases: Focus on Human Liver Cells

  • Sascha Venturelli
  • Christian Leischner
  • Markus Burkard
Reference work entry

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.

Keywords

Flavonoid Flavonol Kaempferol Quercetin Hepatocellular carcinoma Primary human hepatocytes Pan-HDAC inhibitor Cytochrome p450 enzymes Liver Phase I metabolism 

List of Abbreviations

B[a]P

Benzo[a]pyrene

CDK1

Cyclin-dependent kinase 1

CYP

Cytochrome P450

DMBA

7,12-Dimethylbenz[a]anthracene

DNMT

DNA methyl transferase

GSTP1–1

Glutathione S-transferase Pi 1 peptide 1

HAT

Histone acetyl transferase

HCC

Hepatocellular carcinoma

HDAC

Histone deacetylase

PHH

Primary human hepatocyte

P-PST

Phenol-sulfating form of phenol sulfotransferase

QR

Quinone reductase

SAHA

Suberoylanilide hydroxamic acid

SIRT

Sirtuin

SULT1A1

Sulfotransferase family 1A Member 1

SULT1E1

Sulfotransferase family 1E Member 1

TCDD

2,3,7,8-Tetrachlorodibenzo-p-dioxin

TSA

Trichostatin A

TS-PST

Thermostable phenol sulfotransferase

UDP

Uridine diphosphate

UGT

UDP-glucuronyl transferase

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sascha Venturelli
    • 1
  • Christian Leischner
    • 1
  • Markus Burkard
    • 1
  1. 1.Department of Vegetative and Clinical Physiology, Institute of PhysiologyUniversity Hospital TuebingenTuebingenGermany

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