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

Abstract

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 r esol v ins of the E series (resolvin E1 or RvE1), and those biosynthesized from the precursor DHA are denoted r esol v ins of the D series (resolvin D1 or RvD1). The number 1 designates the bioactive compounds in this family (e.g., 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 17 R‐D series resolvins and docosatrienes. These epimers are denoted as aspirin‐triggered (AT)‐RvD and DT, and possess potent anti‐in‐flammatory actions in vivo essentially equivalent to their 17 S series pathway products. These include five distinct series: (i) 18 R resolvins from EPA (i.e., RvE1); (ii) 17 R series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17 S series resolvins from DHA (RvD1 through RvD4), (iv) DT from DHA; and (v) their AT form 17 R series DT. In this article, we provide an overview of the formation and actions of these newly uncovered pathways and products.