2,3,5,4'-Tetrahydroxy Stilbene-2-O-?-D-Glucoside Ameliorates Imiquimod-induced Psoriasis-Like Skin Iflammation Via IL-36/P2x7R

Scope:2,3,5,4-Tetrahydroxy stilbene-2-O-?-D-glucoside(2354Glu),which is attributed to the root extract,possesses multiple pharmacological activities.Since,regulating immune response and P2x7R-NLRP3 inflammasome activation with small molecule inhibitors might be a potential therapeutic strategy to treat and prevent skin psoriasis,we investigated whether this process would be modulated by 2354Glu.Methods:Mice were injected with 2354Glu(100 or 25mg/kg)or cover DSMS cream 450?g for 8 days,cover imiquimod cream from the 5th day.Observed the back skin histomorphological changes by HE staining The expression of factors related with psoriasis marker and inflammasome such as IL-36a?IL-36??IL-36??IL-l?and P2x7 were measured by Western bolt;and psoriasis marker IL-36yKeratin1?Keratin14?PCNA,macrophages marker F4/80?Mac-3?Ly-6C/Ly-6G and protein related P2x7R-NLRP3 inflammasome such as Caspase-1?NLRP3 were measured by Immunohistochemistry or qPCR;and the toxicity of 2354Glu was tested in vitro by mesuring epidermal skin thickness and level of PCNA,in vivo by MTT Assay on HepG2 cells?HaCat and mice primary keratinocytes.Results:In vitro,2354Glu has nontoxic to mice skin,and has no defect on HepG2 cells?HaCat and mice primary ketatinocytes cell viability.In mice model of imiquimod induced skin psoriasis,2354Glu significantly decreased epithelium hyperplasy,small Munro abscesses,dyskeratosis and acanthosis.The expression of protein such as Proliferating cell nuclear antigen?Keratinel and Keratine 14 were decreased.2354Glu regulates the level of skin psoriasis marker protein and mRNA IL-36?.Effectively blocked IL-1? production and caspase-1 activation,as well as NLRP3 and P2x7R protein expression.In addition 2354Glu treatment regulated transmembrane adhesion glycoprotein(F4/80)?neutrophils and eosinophils(Ly-6C/Ly-6G),and regulate immune response.Conclusion:2354GLu might be mediated P2x7R-NLRP3 inflammasome and regulate immune effector cells to inhibit the expression of psoriasis marker IL-36 to improve skin injury.