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Kaempferol attenuates 4-hydroxynonenal-induced apoptosis in PC12 cells by directly inhibiting NADPH oxidase.

Abstract
Kaempferol, a natural flavonoid isolated from various plant sources, has been identified as a potential neuroprotectant. In this study, we investigated the protective effect of kaempferol against 4-hydroxynonenal (HNE)-induced apoptosis in PC12 rat pheochromocytoma cells. Kaempferol inhibited 4-HNE-mediated apoptosis, characterized by nuclear condensation, down-regulation of antiapoptotic protein Bcl-2, and activation of proapoptotic caspase-3. Kaempferol inhibited 4-HNE-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). More importantly, kaempferol directly bound p47(phox), a cytosolic subunit of NADPH oxidase (NOX), and significantly inhibited 4-HNE-induced activation of NOX. The antiapoptotic effects of kaempferol were replicated by the NOX inhibitor apocynin, suggesting that NOX is an important enzyme in its effects. Our results suggest that kaempferol attenuates 4-HNE-induced activation of JNK and apoptosis by binding p47(phox) of NOX and potently inhibiting activation of the NOX-JNK signaling pathway in neuron-like cells. Altogether, these results suggest that kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration.
AuthorsYoung Jin Jang, Jiyoung Kim, Jaesung Shim, Jaekyoon Kim, Sanguine Byun, Min-Ho Oak, Ki Won Lee, Hyong Joo Lee
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 337 Issue 3 Pg. 747-54 (Jun 2011) ISSN: 1521-0103 [Electronic] United States
PMID21398514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetophenones
  • Aldehydes
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Indoles
  • Kaempferols
  • Neuroprotective Agents
  • DAPI
  • kaempferol
  • acetovanillone
  • NADPH Oxidases
  • JNK Mitogen-Activated Protein Kinases
  • Trypan Blue
  • 4-hydroxy-2-nonenal
Topics
  • Acetophenones (pharmacology)
  • Aldehydes (pharmacology)
  • Animals
  • Apoptosis (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Fluorescent Dyes (metabolism)
  • Indoles (metabolism)
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Kaempferols (agonists, pharmacology)
  • NADPH Oxidases (antagonists & inhibitors, metabolism)
  • Neurons (drug effects, enzymology, physiology)
  • Neuroprotective Agents (analysis, pharmacology)
  • PC12 Cells
  • Phosphorylation
  • Rats
  • Trypan Blue (metabolism)

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