Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor

Free Radic Biol Med. 2017 Sep:110:176-187. doi: 10.1016/j.freeradbiomed.2017.06.006. Epub 2017 Jun 9.


Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q10, but due to its highly lipophilic nature, Q10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney.

Keywords: 4-hydroxybenzoic acid; Antioxidants; Coenzyme Q; Flavonols; Kaempferol; Kidney cells; Plant polyphenols; Sirt3.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Carbon Isotopes
  • Cell Line
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / enzymology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • HEK293 Cells
  • HL-60 Cells
  • Hep G2 Cells
  • Humans
  • Isotope Labeling
  • Kaempferols / pharmacology*
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / enzymology
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Polyphenols / pharmacology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / growth & development
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism
  • Ubiquinone / biosynthesis*


  • Antioxidants
  • Carbon Isotopes
  • Kaempferols
  • Polyphenols
  • Ubiquinone
  • kaempferol
  • SIRT3 protein, human
  • Sirtuin 3