Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid
Article first published online: 1 MAR 2004
Journal of Neurochemistry
Volume 89, Issue 2, pages 484–493, April 2004
How to Cite
Wenk, G. L., McGann-Gramling, K., Hauss-Wegrzyniak, B., Ronchetti, D., Maucci, R., Rosi, S., Gasparini, L. and Ongini, E. (2004), Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid. Journal of Neurochemistry, 89: 484–493. doi: 10.1111/j.1471-4159.2004.02359.x
- Issue published online: 22 MAR 2004
- Article first published online: 1 MAR 2004
- Received October 31, 2003; revised manuscript received December 18, 2003; accepted December 19, 2003.
- Alzheimer's disease;
- ferulic acid;
- NCX 2057;
- nitric oxide
Chronic neuroinflammation and oxidative stress contribute to the neurodegeneration associated with Alzheimer's disease and represent targets for therapy. Ferulic acid is a natural compound that expresses antioxidant and anti-inflammatory activities. Nitric oxide is also a key modulator of inflammatory responses. Grafting a nitric oxide-releasing moiety onto anti-inflammatory drugs results in enhanced anti-inflammatory activity. We compared the effectiveness of ferulic acid with a novel nitric oxide-releasing derivative of ferulic acid in an animal model of chronic neuroinflammation that reproduces many interesting features of Alzheimer's disease. Lipopolysaccharide was infused into the 4th ventricle of young rats for 14 days. Various doses of ferulic acid or its nitric oxide-releasing derivative were administered daily. Both drugs produced a dose-dependent reduction in microglia activation within the temporal lobe. However, the nitric oxide-releasing ferulic acid derivative was significantly more potent. If we delayed the initiation of therapy for 14 days, we found no reduction in microglial activation. In addition, both drugs demonstrated antioxidant and hydroxyl radical scavenging abilities in in vitro studies. Overall, our results predict that a treatment using nitric oxide-releasing ferulic acid may attenuate the processes that drive the pathology associated with Alzheimer's disease if the treatment is initiated before the neuroinflammatory processes can develop.