Fig. 2

Eicosanoid families of omega-3 and omega-6 polyunsaturated fatty acids involved in intestinal inflammation and resolution. Eicosanoids are predominantly generated from the ω-6 arachidonic acid (ARA) in phospholipid cell membranes by the enzymatic actions of cyclooxygenase (COX) and lipoxygenase (LOX). The COX pathway generates 2-series prostaglandins (PGs) and thromboxanes (TXBs), while the LOX generates lipoxins (LXs), hydroxyeicosatetraenoic acids (HETEs) and, 4-series leukotrienes (LTs) that occasionally stimulates excessive pro-inflammatory response leading to chronic intestinal inflammatory diseases. On the other hand, the ω-3 eicosapentaenoic acid (EPA) stimulates acute inflammation by generating 3-series PGs and TXBs via the COX pathway, while hydroxyeicosapentaenoic acids (HEPEs) and 5-series LTs via the LOX pathway. Recently, certain ARA-derived PGs and LXs were identified to exert both pro-inflammatory and pro-resolution characteristics. Similarly, the newly identified downstream molecules of EPA such as the E-series resolvins (RvEs) and docosahexaenoic acid (DHA) such as the D-series resolvins (RvDs), maresins (MaRs), and protectins (PDs) are involved in pro-resolution. Both ω-3 and ω-6 polyunsaturated fatty acids (PUFA) supports pro-resolution, but overwhelming data reported ω-3 PUFA as the strongest anti-inflammatory agent. This could be due to the difference in magnitude of action among the eicosanoids involved in the resolution phase of inflammation. For references, see text. Figure created using BioRender.com