Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases

Abstract

Inflammation is an a physiological response instead an essential response of the organism to injury and its adequate resolution is essential to restore homeostasis. However, defective resolution can be the precursor of severe forms of chronic inflammation and fibrosis. Nowadays, it is known that an excessive inflammatory response underlies the most prevalent human pathologies worldwide. Therefore, great biomedical research efforts have been driven toward discovering new strategies to promote the resolution of inflammation with fewer side-effects and more specificity than the available anti-inflammatory treatments. In this line, the use of endogenous specialized pro-resolving mediators (SPMs) has gained a prominent interest. Among the different SPMs described, lipoxins stand out as one of the most studied and their deficiency has been widely associated with a wide range of pathologies. In this review, we examined the current knowledge on the therapeutic potential of lipoxins to treat diseases characterized by a severe inflammatory background affecting main physiological systems, paying special attention to the signaling pathways involved. Altogether, we provide an updated overview of the evidence suggesting that increasing endogenously generated lipoxins may emerge as a new therapeutic approach to prevent and treat many of the most prevalent diseases underpinned by an increased inflammatory response.

Resolvins, Protectins, and Maresins: DHA-Derived Specialized Pro-Resolving Mediators, Biosynthetic Pathways, Synthetic Approaches, and Their Role in Inflammation

“…Lipoxins (LXs) result from a biosynthetic pathway of omega-6 fatty acid: araquidonic acid. LXs were the first SPM to be described and studied due to their essential role in various inflammatory diseases [ 25 ]. Resolvins from EPA (E-resolvins) and from DHA (D-resolvins) and protectins and maresins from DHA are structurally distinct from LXs resulting from a different metabolic pathway from omega-3 fatty acids.…”

“…MaR-1 and Mar-2 are produced by enzymatic hydrolysis with epoxide hydrolase and with soluble epoxide hydrolase (sHE), respectively, as depicted in Scheme 31 . [ 25 , 40 , 77 , 85 , 86 , 89 , 90 ].…”

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

“…These partially oxidized lipidic compounds, oxylipins, may participate in the activation of anti-inflammatory processes and the clearance of cellular debris as well as inhibit numerous proinflammatory cytokines [90]. Additionally, EET, and other epoxy fatty acids, stimulate the production of specialized proresolving mediators (SPMs), such as lipoxins, by shifting ARA metabolism, to support inflammation resolution [91]. In addition to omega-6 arachidonic acid-derived lipoxins, n-3 PUFA-derived SPMs are synthesized from EPA and docosahexaenoic acid and encompass resolvins, protectins, and maresins [76,92].…”

Whole-plant foods and their macromolecules: untapped approaches to modulate neuroinflammation in Alzheimer’s disease

“…The inflammatory conditions in activated microglia have been found to be regulated by intracellular signaling pathways, mainly by NF-κB and MAPK pathways (Leng and Edison 2021). Also, LXA4 is an endogenous anti-inflammatory molecule that could modulate the levels of various transcription factors such as NF-κB (Jaén et al 2021). In the following section, we comprehensively summarize and discuss the LXA4-NF-κB and MAPK pathways in the inflammatory processes, which are conducive to revealing some insights on the mechanism of AD.…”