Maresin

Dalli, 1., M. Zhu et al. 2013. The novel 13S,14S-epoxy-maresin is converted hy human macrophages to maresin 1 (MaRl), inhihits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype. FASEB 27(7) 2573-2583. 

Notdgien, T. M., A. J. Heires et al. 2013. Maresin-1 reduces the pro-inflammatory response of hronchial epithelial cells to organic dust. 14(1) 51. 

Serhan, C. N., J. Dalh et al. 2012. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. 26(4) 1755—1765. 

Marcon R., Bento A. E, Dutra R. C., Bicca M. A., Leite D. F. R, CaUxto J. B. 2013. Maresin 1, a proresolving Upid mediator derived from omega-3 polynnsaturated fatty acids, exerts protective actions in murine models of colitis. 

More recent applications of the Sonogashira reaction in PUFA synthesis include Spurs and Rodriguez s synthesis of maresin 1 (56) [72], a potent anti-inflammatory lipid mediator derived from DHA (7). As shown in Scheme 3.21, the Sonogashira cross coupling reaction of alkyne 82, bearing an unprotected secondary alcohol, with vinyl iodide 83, provided compound 84. Then, removal of the TES group, Boland reduction of the triple bond, and subsequent hydrolysis of the methyl ester afforded maresin 1 (56). 

A number of PUFA products are generated through sequential LOX reactions and transcellular metabolism involving multiple enzymes that may be native to different cell types (Sala et al. 2010). These reactions generate poly-hydroxy fatty acids such as lipoxins, resolvins, protectins, and maresins, products of AA, EPA, and DHA... 

Serhan, C. N., R. Yang et al. 2009. Maresins Novel macrophage mediators with potent antiinflammatory and proresolving actions. J c M 206(1) 15—23. 

Beneficial Roles of Lipoxins, Resolvins, Protectins, and Maresins.185... 

This chapter summarizes recent findings involving the formation and biological roles of several new types of polyunsaturated anti-inflammatory and pro-resolving lipid mediators [1], such as lipoxins, resolvins, protectins, and maresins (MaR). These molecules are able to dampen the inflammatory response, promote the resolution of inflammation, and exhibit other beneficial actions at inflammatory sites [2-4]. 

DHA, a C22 6 omega-3 (co-3) fatty acid, is a major lipid component in the brain and eye [14], and a common ingredient of fish oil. DHA is an extensively stndied PUFA, and its enzymatic oxygenation leads to several series of benehcial lipid mediators (docosanoids), including D-resolvins (RvD) [15], protectins/nenroprotectins (PD/NPD) [16-19], and maresins (MaR) [20-22]. 

This chapter is focused on the biosynthesis and actions of lipoxins, resolvins, protectins, and maresins. Each group of PUFA-derived lipid mediators has its own distinct biosynthetic pathways and features a specialized biological activity profile. 

A large number of studies on the biological actions of the lipoxins and their stable analogs revealed the multi-faceted biological roles of this class of lipid mediators [8,10,11,27,28,30,31,35,37-63], Selected examples of applications in various disease models are summarized in the section Beneficial Roles of Lipoxins, Resolvins, Protectins, and Maresins (Table 9.1). 

The maresins (MaR) are lipid mediators generated from DHA in macrophages and have beneficial actions by enhancing resolution. The name maresin was coined to indicate that they are macrophage mediators that raolve inflammation [20]. 

While the biological roles of the maresins are still under investigation, some distinct activities have been described [20-22,63,96], including several disease models (Table 9.1). 

The lipid mediators derived from ARA, EPA, and DHA discussed above (i.e., lipox-ins, resolvins, protectins, and maresins) have different biosynthetic origins and variable overall bioactivity profiles. These molecules have been collectively termed specialized pro-resolving lipid mediators (SPM), due to their conunon biological role, namely their ability to reduce the inflanunatory response, and to promote the resolution of inflammation and return to homeostasis. 

Maresins Novel macrophage mediators with potent antiinflammatory and proie-solving actions. 206(l) 15-23. 

SCHEME 341 A brief overview of the biosynthesis of the resolvins, maresins, and protectins [63]. 

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