2-4-dinitrofluorobenzene-sulfonic-acid and glyceryl-2-arachidonate

Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a drug-carrier conjugate between PEA (the active drug) and glucuronic acid (the carrier). The conjugate, named GLUPEA, was characterized for its capability of increasing PEA levels and exerting anti-inflammatory activity both in vitro and in vivo. GLUPEA treatment, compared to the same concentration of PEA, resulted in higher cellular amounts of PEA and the endocannabinoid 2-arachidonoyl glycerol (2-AG), and increased 2-AG-induced transient receptor potential vanilloid type 1 (TRPV1) channel desensitization to capsaicin. GLUPEA inhibited pro-inflammatory monocyte chemoattractant protein 2 (MCP-2) release from stimulated keratinocytes, and it was almost as efficacious as ultra-micronized PEA at reducing colitis in dinitrobenzene sulfonic acid (DNBS)-injected mice when using the same dose. GLUPEA is a novel pro-drug able to efficiently mimic the anti-inflammatory and endocannabinoid enhancing actions of PEA.

Topics: Amides; Animals; Arachidonic Acids; Calcium; Chemokine CCL8; Colitis; Colon; Dinitrofluorobenzene; Drug Delivery Systems; Endocannabinoids; Ethanolamines; Glucuronic Acid; Glycerides; HaCaT Cells; HEK293 Cells; Humans; Ion Channel Gating; Keratinocytes; Male; Mice, Inbred ICR; Models, Biological; Palmitic Acids; Peroxidase; Poly I-C; TRPV Cation Channels