Kaempferol, a natural flavonoid isolated from various plant sources, has been identified as a potential neuroprotectant. Here, 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 anti-apoptotic protein Bcl-2 and activation of pro-apoptotic caspase-3. Kaempferol inhibited 4-HNE-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). Importantly, kaempferol directly bound p47phox, a cytosolic subunit of NADPH oxidase (NOX), and significantly inhibited 4-HNE-induced activation of NOX. The anti-apoptotic 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 the p47phox of NOX and potently inhibiting activation of NOX-JNK signaling pathway in neuron-like cells. Altogether, these results suggest that kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration.
- Received November 29, 2010.
- Revision received March 9, 2011.
- Accepted March 10, 2011.
- The American Society for Pharmacology and Experimental Therapeutics