| Research objectives:1.To explore the drug action targets of Yuhuang ointment in the treatment of blood stasis evidence of plaque psoriasis.2.To reveal the efficacy characteristics of Yuhuang ointment in the treatment of blood stasis in plaque psoriasis in terms of clinical and immune mechanisms,and to verify the therapeutic mechanism of Yuhuang ointment.Research methods:This study was divided into two parts:1.Network pharmacology study:Based on the pharmacology platform of the TCM system and literature mining,the main five herbs in Yuhuang ointment were searched with keywords to obtain their chemical composition and ADME condition screening,setting the screening condition as drug-like(drug-likeness,DL)≥ 0.18,to obtain the active compounds and their protein targets of action.This was supplemented by published literature reports.The predicted targets were translated into standard gene names using the UtiProt protein database.Using "Psoriasis" as a keyword,we searched several disease databases such as GeneCards to obtain the potential targets for psoriasis and thus established a psoriasis target dataset.By constructing the"drug-component-target-disease" network of Yuhuang ointment through Cytoscape software and establishing the protein interaction network using the STRING online platform,we used the DAVID database to analyze the biological processes and signaling pathways of the targets of Yuhuang ointment and screen out the possible drug targets of Yuhuang ointment.2.Clinical trial study:Patients aged 18 to 65 years old with plaque psoriasis and TCM evidence of blood stasis were enrolled according to the established nadir criteria.Based on the targets screened by network pharmacology,peripheral venous blood samples were collected from all patients before the start of treatment to measure the expression of serum IL-17A and K17.All patients received standardized topical treatment with Yuhuang ointment for 4 weeks and were visited at 0,2,and 4 weeks of treatment to assess the disease severity score(PASI score),target lesion score,and lesion-symptom score(erythema mean score,scaling mean score,and infiltration mean score).The differences in the efficacy of Yuhuang ointment at different IL-17A and K17 expression levels were compared,and the evaluation indexes included the efficacy index(rate of decrease in PASI score),the rate of decrease in target lesion score,and the improvement in the severity of lesion symptoms(PGA score decline rate<50%was considered as moderate improvement,PGA score decline rate ≥50%was considered as significant improvement),and the differences between groups were compared by statistical methods.Results of the study:1.In this study,a total of 273 active ingredients and 412 action targets of Yuhuang ointment were screened,and the drugs with the most target activity were quercetin,the active ingredient of licorice,followed by dahurica,angelica,and turmeric common ingredient dousterol,aromatic curcuminoids and curcumin in turmeric and rhamnose in angelica.Among them,207 targets intersected with psoriasis disease targets,and GO functional enrichment analysis and KEGG signaling pathway enrichment analysis were performed for the 207 intersected targets,and a total of 20 biological processes were obtained,which involved cellular response to cytokine stimulation,inflammatory response,positive regulation of cell migration,cell activation,cellular response to growth factor stimulation,etc.;KEGG pathway analysis yielded a total of 20 related pathways.The results showed that module a involved the JAK-STAT signaling pathway,IL-17 signaling pathway,and T cell receptor signaling pathway;module b involved the JAK-STAT signaling pathway,PI3K-Akt signaling pathway,and P53;module c involves cell cycle,cell aging and T cell receptor signaling pathway.These pathways are involved in the inflammatory response and keratinocyte proliferation in psoriasis.IL-17 signaling pathway is highly correlated with psoriasis,and K17 is the keratin specifically and highly expressed in psoriasis epidermal keratinocytes.Therefore,it is speculated that the inflammatory factor represented by IL-17 and the specific marker of keratinocyte overexpression represented by K17 are the key observation indexes for Yuhuang ointment in the treatment of psoriasis.2.A total of 53 patients with blood stasis evidence of plaque psoriasis were included in this study.(1)After treatment,the PASI score,target lesion score,and lesion-symptom score(erythema mean score,scale mean score,and infiltration mean score)of the patients decreased significantly(P<0.05)compared with before.Among them,the improvement of erythema mean score,scale mean score,and infiltration mean score were statistically different among the three groups(P=0.036).21.4%of patients had significant improvement in erythema mean score,47.7%of patients had significant improvement in scale mean score,and 40.5%of patients had significant improvement of infiltration mean score.(2)IL-17A expression differed between groups with different severity of lesion-symptom scores,with IL-17A expression significantly higher in both the high mean score of scales/medium mean group than in the low mean group(P=0.043,P=0.004)and the high mean group of infiltrates than in the medium mean group of infiltrates/low mean group(P=0.046,P=0.002),and erythema The expression of IL-17A was not statistically different between groups with different severity of homogeneous scores.(3)The expression of K17 was significantly higher in patients with psoriasis than in the healthy population(P<0.05),and the expression of K17 was significantly higher in different emission-symptom scores(erythema mean score,scale mean score,infiltration mean score)than in the healthy population(P<0.05),but there was no statistical difference in the expression of K17 between different severity of session-symptom scores groups.(4)There was a linear correlation trend between the expression of K17 and the efficacy index and the decreased rate of target skin lesion score at 2 weeks and 4 weeks of treatment,respectively(P>0.05);however,the linear correlation trend between the expression of IL-17A and the treatment efficiency of Yuhuang ointment before was not significant(P>0.05).(5)The expression of IL-17A was not statistically different between groups in the improvement of lesion symptoms(erythema,scaling,infiltration mean score)(P=0.308,P=0.260,P=0.152).the expression of K17 was not statistically different between groups in the improvement of lesion symptoms(erythema,infiltration mean score)(P=0.167,P=0.614),the expression of K17 was not statistically different between groups in the improvement of lesion There a trend of difference between groups in the improvement of symptomatic scaling mean scores(P=0.075).Study conclusion:Yuhuang ointment can significantly improve the severity of psoriasis disease,and lesion-related symptoms(scaling,infiltration,erythema),and the degree of improvement against scaling and infiltration is significantly better than that of erythema,suggesting that there is an efficacy difference between Yuhuang ointment in improving lesion-related symptoms,and Yuhuang ointment is more able to play a therapeutic role against scaling and infiltration.Serum IL-17 levels were more correlated with the severity of psoriasis lesion-related symptoms(scaling and infiltration),with the more severe the scaling/infiltration,the higher the serum IL-17 level.Serum IL-17 levels did not correlate with the PASI decline rate and target lesion score decline rate of Yuhuang ointment,suggesting that Yuhuang ointment may not exert its therapeutic effect by directly affecting IL-17 expression.The expression level of serum K17 was significantly higher than that of a healthy population,and the expression level of serum K17 was similar for different severity of scaling and infiltration of psoriasis.It is suggested that psoriasis scaling and infiltration may represent the indirect initiating factors affecting the high expression of serum K17,but the severity did not affect the serum K17 level.The study also showed that the expression level of serum K17 and the treatment efficiency of Yuhuang ointment showed a difference in the treatment time,showing a trend of lower and then higher,which may be related to the activation of IL-17 signaling pathway and the dynamic change of IL-17 expression after treatment.The above findings suggest that although Yuhuang ointment could not affect the expression of IL-17,it may have affected the expression of K17 by interfering with the IL-17-mediated signaling pathway,thus improving the severity of lesions and scaling score,infiltration score and exerting the therapeutic effect of moistening and eliminating plaques. |
PDF Full Text Request