Study On Anti-psoriasis Effect And Mechanism Of Ar-turmerone

Psoriasis is a common type of scaly and papular dermatosis with the abnormal proliferation of keratinocytes as characteristic,which is a chronic immune inflammatory disease.The morbidity of psoriasis is 0.1-3 % in the worldwide,2-3 % in occident and 0.4 %(about 5 million)in our country,but quite different in each state.Patients of psoriasis have a characteristic that a longer course of disease,easy to relapse,some cases almost never heals.Moreover,psoriasis patients is susceptible to other diseases,such as psoriatic arthritis,anxiety,depression,lymphoma and metabolic syndrome,impact to patients’ health and spirit.The research and development of new drugs on psoriasis has made a great progress in recent years,they are targeted to tumor necrosis factor-alpha(TNF-α),Janus kinase(JAK),interferon(IFN),interleukin(IL)and interleukin receptor(ILR)which are related to immunization and inflammation.Multiple drugs on these targets are listed and entered clinical study,but the efficacy and side-effects are not satisfied.Because of these,developing a higher effective and lower toxic anti-psoriasis drugs is still a hot spot.Ar-turmerone(ATM)has a good effect on anti-tumor,anti-inflammatory and anti-oxidant,is the mainly component of curcuma oil.The mechanism of ATM on anti-inflammatory is impacted the activity of NF-κB pathway and the expression of inflammatory factors,including TNF,IL and IFN by regulated the phosphorylation of JNK,p38 MAPK,ERK1/2 and the activity of PI3K/AKT pathway.The application of ATM on inflammation attracts our research group’s interesting.Based on a research of literature about psoriasis and ATM,with a goal on anti-psoriasis,the aim of this thesis was study the effect and mechanism of ATM on anti-psoriasis.In our work,the isolated,purification and structure identification of ATM,the study of interacting between ATM and targets of psoriasis,and the effect and mechanism of ATM on anti-psoriasis were included.The main works and results in this thesis are shown as follow:(1)Reviews on the mechanism and drugs of psoriasis,and summarizes the isolation,purification and bio-activity of ATM.(2)ATM was separated from curcuma oil,and the structure and purty were identificated.The column chromatography was used to enrichment of ATM firstly,and then reversed-phase preparative liquid chromatography was applied.The ATM sample was got after extracted by petroleum ether and removing solvent.The information of ATM in samples was confirmed by nuclear magnetic resonance(NMR),mass spectrum(MS)and high performance liquid chromatography(HPLC),showed the content was 98.62 %(3)The effect of ATM inhibited imiquimod(IMQ)-induced psoriasis model was study.A model of psoriasis induced by IMQ was built,and the effect of ATM on reduced IMQ-induced psoriasis-like skin damage and hyperkeratosis were proved by PASI and hematoxylin-eosin(H&E)staining.ATM inhibited the cells proliferation and increasing thickness in epidemic,and protected the skin barrier.(4)The mechanism of ATM inhibited the psoriasis was study.Searched and arranged the information of targets on psoriasis,and the crystal structure was obtained from RCSB protein bank database.The Surflex-Dock program integrated in Sybyl software was used,and seventeen models of targets on psoriasis was built,and then structure of ATM was docked with each optimized target respectively.As a result,two potential targets named TLR7 and p38 MAPK were found.The next step,the content of CD8+ T cells,COX-2 and NF-κB in epidermis were measured by immunohistochemistry(IHC),proved ATM inhibited the increasing content of CD8+ T cells effectively,reduced the production of COX-2 but not affected the expression of NF-κB.The expression of related immunological factors and the phosphorylation of related kinases were observed by Western Blotting,and it found that ATM inhibited the phosphorylation of p38 MAPK and the expression of NF-κB in skin,up-regulated the secretion of IL-1β and reduced the expression of IFN-γ,IL-6 and TNF-α.The fluorescent quantitative PCR was used to measure the transcription level on immunological factors related to psoriasis,showed ATM inhibited the transcription of IFN-α,both IL-17 and IL-22 had a certain inhibitory effect on transcription and the synthetic mRNA on IL-12 and IL-23 were regulated by ATM,suggested ATM has an immunomodulatory effect on IMQ-induced psoriasis-like skin.