resolvin d1

Resolvin D1 (RvD1) is an endogenous pro-inflammatory mediator that blocks pro-inflammatory neutrophil migration by regulating actin polymerization, reduces TNF-α-mediated inflammation in macrophages, and enhances macrophage phagocytosis of apoptotic cells.

Resolvins are a family of potent lipid mediators derived from both eicosapentaenoic acid and docosahexaenoic acid.[1] In addition to being anti-inflammatory, resolvins promote the resolution of the inflammatory response back to a non-inflamed state.[2] Resolvin D1 is produced physiologically from the sequential oxygenation of DHA by 15- and 5-lipoxygenase.[1] 17(R)-RvD1 is an aspirin-triggered epimer of RvD1 that reduces human polymorphonuclear leukocyte (PMN) transendothelial migration, the earliest event in acute inflammation, with equipotency to RvD1 (EC50 = ~30 nM).[3] 17(R)-RvD1 exhibits a dose-dependent reduction in leukocyte infiltration in a mouse model of peritonitis with maximal inhibition of ~35% at a 100 ng dose.[3] In contrast to RvD1, the aspirin-triggered form resists rapid inactivation by eicosanoid oxidoreductases. Analytical and biological comparisons of synthetic 17(R)-RvD1 with endogenously derived 17(R)-RvD1 have confirmed its identity as matching the natural product.[4]

Resolvin D1 is produced physiologically from the sequential oxygenation of docosahexaenoic acid by 15- and 5-lipoxygenase . It reduces human polymorphonuclear leukocyte transendothelial migration, the earliest event in acute inflammation, with an EC50 value of ~30 nM. RvD1 methyl ester is a methyl ester version of the free acid that may act as a lipophilic prodrug form that will alter its distribution and pharmacokinetic properties. The methyl ester moiety is susceptible to cleavage by intracellular esterases, leaving the free acid.

Benzo-resolvin D1 (benzo-RvD1), a derivative of the specialized pro-resolving mediator (SPM) RvD1, effectively reduces PDGF-BB-induced cytoskeletal alterations and PDGF-triggered migration in isolated human vascular smooth muscle cells (VSMCs) at 10 and 100 nM concentrations. Additionally, at a 10 nM concentration, benzo-RvD1 inhibits p65 nuclear translocation in human umbilical vein endothelial cells (HUVECs) and enhances phagocytosis of S. aureus and zymosan particles by RAW 264.7 cells.

17(R)-Resolvin D1 (17(R)-RvD1) is an aspirin-triggered epimer of RvD1 that equivalently inhibits human polymorphonuclear leukocyte migration across the endothelium (EC50= ~30 nM), a precursor to acute inflammation. Unlike RvD1, it resists rapid degradation by eicosanoid oxidoreductases. In a mouse peritonitis model, 17(R)-RvD1 dose-dependently reduces leukocyte infiltration, achieving up to a 35% decrease with a 100 ng dose. Additionally, its methyl ester derivative, designed to enhance its pharmacokinetic and distribution properties as a more lipophilic prodrug, can be converted back into the active acid form by intracellular esterases.

NCGC00135472 (DRV1 (GPR32) agonist C2A) is a human Resolvin DI receptor DRV1 agonist with pro-catabolic properties that activates the human soluble protein D1 receptor DRV1/GPR32 receptor in beta-blocker and cAMP assays with EC50s of 0.37 uM and 0.05 uM, respectively.NCGC00135472 induces in cells overexpressing recombinant DRV1 rapid impedance changes that stimulate phagocytosis of serum-treated zymoglycans.