17(R)-Resolvin D1

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]

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.

17(R,S)-Benzo-resolvin D1 (benzo-RvD1) 是专门的分辨介质 (SPM) RvD1 的衍生物。在10和100 nM的浓度下，它能减少PDGF-BB诱导的人类血管平滑肌细胞 (VSMCs) 的细胞骨架变化，并抑制PDGF诱导的这些细胞的迁移。Benzo-RvD1 (10 nM) 抑制人脐静脉内皮细胞 (HUVECs) 中的p65核转位。它还提高了RAW 264.7对S. aureus和zymosan颗粒的吞噬作用。