The Study Of Anti-inflammatory Effect And Mechanism Of 5-hydroxymethylfurfural And Its Application In Wound Healing

Skin wound healing is a challenging medical problem,and it is necessary to design and develop a fast and effective method to cure wounds.Wound healing generally involves four stages,hemostasis,inflammatory response,proliferation and remodeling stage.In general,inflammatory response and cell proliferation are stages that can be artificially intervened and effectively promote wound healing.5-Hydroxymethylfurfural has a variety of beneficial biological functions,such as anti-oxidation,anti-hypobaric hypoxia and cardioprotective,but little literature focus on its anti-inflammatory and application in wound healing.In this study,the anti-inflammatory effect and pharmacological mechanism of 5-hydroxymethylfurfural were investigated.The effect and mechanism of 5-hydroxymethylfurfural on wound healing in vitro and in vivo were investigated using the polyvinyl alcohol/alginate hydrogel carrier.1.In this study,we investigated the anti-inflammatory activity of 5-hydroxymethylfurfural and its underlying mechanisms in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.The results showed that 5-hydroxymethylfurfural reduced the expression levels of nitric oxide(NO),prostaglandin E2(PGE2)and proinflammatory cytokines(TNF-?,IL-1? and IL-6)in a concentration-dependent manner.5-hydroxymethylfurfural-pretreated cells significantly downregulated the mRNA expression of two major inflammatory mediators,nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)and suppressed the production of pro-inflammatory cytokines.5-hydroxymethyl inhibited the phosphorylated expression levels of extracellular regulated protein kinase(ERK1/2),c-Jun N-terminal kinase(JNK),I?B?,NF-?B p65,rapamycin mammalian target protein(mTOR)and protein kinase B a protein(Akt)to exert the anti-inflammatory effect.In addition,5-hydroxymethylfurfural has been shown to inhibit NF-?B p65 translocation to the nucleus to activate inflammatory gene transcription.These results indicate that 5-hydroxymethylfurfural exerts anti-inflammatory activity through inhibiting the expression of MAPK,NF-?B and Akt/mTOR signal pathway proteins.2.The effect of 5-hydroxymethylfurfural on wound healing in vitro was assessed through cell proliferation assay,scratch test and transwell chamber migration assay,and measuring collagen content.The results showed that 5-hydroxymethylfurfural could promote the skin fibroblasts proliferation and accelerate the migration.The expression levels of protein and mRNA of collagen significantly increased while treating with 5-hydroxymethylfurfural,indicating that 5-hydroxymethylfurfural has the ability to promote wound repair.3.Through the preparation and characterization of the hydrogel,the optimal ratio of the hydrogel was selected as the carrier for drug delivery.At the same time,the cell biocompatibility was evaluated and using the rat to evaluate the effect of hydrogel loaded with 5-HMF on wound healing.The results showed that the polyvinyl alcohol/sodium alginate hydrogel had good mechanical properties and biocompatibility,while in vivo experiments(animal wound healing rate and pathological tissue section analysis)showed that the poly vinyl alcohol / sodium alginate hydrogel loaded with 5-hydroxymethylfurfural can promote wound healingConclusions: 5-Hydroxymethylfurfural exerted the anti-inflammatory effects through inhibiting MAPK,NF-?B and Akt/mTOR signal pathway proteins.It also could promote the skin fibroblast proliferation and migration.The polyvinyl alcohol/alginate hydrogels possess good biocompatibility,excellent Physicochemical properties,and could accelerate the wound healing.