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It is well known that arachidonic acid is the precursor to potent mediators. Many clinical studies suggest that omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid have beneficial actions in human diseases. The molecular basis of these actions remains of interest.These demonstrate that eicosapentaenoic acid and docosahexaenoic acid are precursors to potent (nM range) bioactive mediators that possess both anti-inflammatory and protective properties. These mediators were coined resolvins, docosatrienes, and protectins as general classes, since each possesses unique chemical structures that are features of the new chemical classes and are biosynthesized by new pathways. Resolvins, discovered first, were identified during the resolution phase of acute inflammation; hence the term resolution interaction products, because they are also biosynthesized by human cells via cell–cell interactions. Docosatrienes contain conjugated triene structures generated from docosahexaenoic acid as a defining feature. The protectins comprise docosatrienes and resolvins of the D series that are both neuroprotective and anti-inflammatory. Aspirin impacts on these new pathways by triggering formation of their epimers (i.e. R isomers).In view of the many beneficial actions attributed to omega-3 dietary supplementation, identification of novel potent mediators from omega-3 that are both anti-inflammatory and protective may have wide implications.