Effect Of Polyphenols Acrylic Derivatives On Dermatitis-eczema And Its Preliminary Mechanism

Objective:Dermatitis-eczema is a inflammation disease whose prevalence has increased considerably in recent years.with the consequent marked effect on patient quality of life.Therefore,it has become a real health problem.In alternative to conventional treatments with corticosteroids and antihistaminics are generally employed, However, they can frequently exhibit a set of undesirable side effects and are not effective in all cases.Thus a new drug which is well effect on dermatitis and low side effeet is badly needed.polyphenolic componds have received considerable interest,because of their broad spectrum of biological activity and low-toxic.In this article, through analyzing the structure-activity relationship,eight novel 3,5-dihydroxycinnamic acid derivatives were synthesized, and their anti-inflammatory activities and preliminary mechanism were evaluated in order to developing a novel NSAIDs.Method:1) 3,5-dihydroxycinnamic acid derivatives was synthesized from 3,5-dihydroxybenzoic acid,through a domino process of multi-pot reaction of methylation, friedel-crafts alkylation,reduction, oxidation, aldol condensation, methylation, esterification and acylation. their anti-inflammatory activities were evaluated using a mouse model of TPA-induced ear edema.2) we evaluated the anti-inflammatory effect of THCA354 on 12-O-tetradecano ylphorbol-13-acetate(TPA), arachidonic acid and xylene induced ear edema in mice in vivo.we investigated hematoxylin and eosin(H&E) stained sections of ear tissue from TPA-treated mice. TPA application resulted in a marked increase in ear thickness and substantial numbers of inflammatory cells infiltrating.The anti-inflammatory mechanism was explored by determining the activity of myeloperoxidase(MPO) and protein levels of inducible tumornecrosis factor-a(TNF-a), interleukin(IL)-1βand IL-6 on TPA induced ear edema model.3) In order to evaluate the influence of THCA354 on allegic immune reaction, a mouse model of allegic contact dermatitis by DNFB was used.The anti-allergy mechanism was explored by determining the protein levels and mRNA expression of inducible tumornecrosis factor-a(TNF-a), interleukin(IL)-1β, IL-6, IL-4, IL-10, IL-17 A, IFN-γ on DNFB induced contact hypersensitivity model.Results:3,5-dihydroxycinnamic acid derivatives was successfully synthesized and separated by recrystallization,All the structures of the compounds were identified by NMR, Ms, IR.Most of derivatives were significantly reduced the TPA-induced ear edema compared With vehicle, the effect of anti-inflammation is THCA354>QJB1-30>THCA357>THCA356>QJB1-31>THCA355,nevertheless,QJB1-28 and QJB1-32 were exhibit no activity.Our results found that topical application of THCA354 could significantly reduced TPA, arachidonic acid and xylene-induced ear edema in mice.Histological analysis also revealed that THCA354 was able to reduce the edema and the influx of inflammatory cells in mice ears.it also could reduced scratching behavior and DNFB-induced contact hypersensitivity.The THCA354 compound treatment also significantly reduced the protein levels of tumor necrosis factor alpha(TNF- α), interleukin-6(IL-6) and IL-1 β and neutrophil-mediated myeloperoxidase activity.Conclusions:THCA354 has significant anti-inflammatory and anti-allergic revealed that THCA354 can be used for dermatitis treatment.Through further study demonstrates that it may be mediated, at least in part,by blocking the neutrophil-mediated myeloperoxidase activity and protein levels of a panel of inflammatory mediators including TNF-a, IL-1β, and IL-6.it also can promote the expression and secretion of inflammation suppression factor,such as IL- 4.