Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers

The molecular basis for the beneficial impact of essential omega-3 (n-3) FA remains of interest. Recently, we identified novel mediators generated from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that displayed potent bioactions identified first in resolving inflammatory exudates and in tissues enriched with DHA. The trivial names resolvin (resolution phase interaction products) and docosatrienes were introduced for the bioactive compounds from these novel series since they possess potent anti-inflammatory and immunoregulatory actions. Compounds derived from EPA carrying potent biological actions (i.e., 1-10 nM range) are designated E series and denoted resolvins of the E series (resolvin E1 or RvE1), and those biosynthesized from the precursor DHA are denoted resolvins of the D series (resolvin D1 or RvD1). The number 1 designates the bioactive compounds in this family (#1-4). Bioactive members from DHA-containing conjugated triene structures or docosatrienes (DT) that possess immunoregulatory and neuroprotective actions were termed neuroprotectins. Aspirin treatment initiates a related epimeric series by triggering endogenous formation of the 17R-D series resolvins and docosatrienes. These epimers are denoted as aspirin-triggered (AT)-RvD and DT, and possess potent anti-inflammatory actions in vivo essentially equivalent to their 17S series pathway products. These include five distinct series: (i) 18R resolvins from EPA (i.e., RvE1); (ii) 17R series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17S series resolvins from DHA (RvD1 through RvD4), (iv) DT from DHA; and (v) their AT form 17R series DT. In this article, we provide an overview of the formation and actions of these newly uncovered pathways and products.