Based On Network Pharmacology And Molecular Docking To Explore The Clinical Efficacy And Mechanism Of Jiedu Lotion For Damp-heat Syndrome Type Lipodermatosclerosis

Objective: Analyzed the main pharmacodynamic mechanism of Jiedu lotion for damp-heat syndrome type lipodermatosclerosis(LDS)through network pharmacology and molecular docking method,clarified the efficacy and molecular mechanism of Jiedu lotion for damp-heat syndrome type LDS through retrospective clinical study and clinical randomized controlled study,so as to verify network pharmacology prediction,provide basis for clinical treatment of damp-heat syndrome type LDS,Promote the modernization of traditional Chinese Medicine.Methods: 1.Network pharmacology research and molecular docking verification: The main bioactive components of Jiedu lotion were screened out from BATMAN-TCM database(score cutoff ? 20 and P ? 0.05),and the corresponding targets were found out;the relevant targets of LDS were screened out by mining Gene Cards,OMIM,TTD and other databases.The targets of Jiedu lotion in the treatment of LDS were obtained by "targets mapping",and the hub targets were screened out by "Network Analyzer" of Cytoscape 3.7.2software.The hub targets were imported into GENEMIANA database to construct PPI network.DAVID database was used for GO function enrichment analysis and KEGG pathway enrichment analysis,to predict the action mechanism of Jiedu lotion in the treatment of LDS.In addition,molecular docking analyses of drug active ingredients-hub targets were used to verify the prediction.2.Retrospective clinical study: Retrospectively analyzed the relevant informations of damp-heat syndrome type LDS patients treated by Jiedu lotion fumigation in our hospital,and analysed the differences of serum TGF-?1,hs-CRP,TNF-? in lower extremity venous blood,CIVIQ,VCSS before and after treatment,so as to find the objective influencing factors and observation indexes for patients with damp-heat syndrome type LDS.Used the Logistic regression analysis to analyze the targets and related influencing factors of Jiedu lotion for damp-heat syndrome type LDS,so as to verify the prediction of network pharmacology.3.Clinical randomized controlled study: 100 cases of damp-heat syndrome type LDS were randomly divided into Jiedu lotion group and control group,50 cases in each group.The Jiedu lotion group was fumigated with Jiedu lotion,once a day;the control group was treated with mucopolysaccharide polysulfate cream,twice a day,for 4 weeks,other treatments were the same.The skin thickness,superficial fascia thickness,deep fascia thickness,skin hardness,skin temperature,VCSS and CIVIQ were monitored before and after treatment to evaluate the clinical efficacy of Jiedu lotion for damp-heat syndrome type LDS.The changes of serum TGF-?1,TNF-? and hs-CRP in Venous blood of lower extremity were detected before and after treatment to explore the molecular mechanism of Jiedu lotion for damp-heat syndrome type LDS,so as to verify the network pharmacology prediction.Result: 1.Network pharmacology research and molecular docking verification: 303 potential compounds and 1481 related targets were extracted from the herbal components of Jiedu lotion.A total of 740 targets related to the pathogenesis of LDS were obtained after gene mining and screening.After targets mapping,166 targets were obtained,and 37 hub targets were screened by network topology analysis,which were mainly enriched in 647 biological processes and 77 signaling pathways(P<0.05).The results of molecular docking showed that the main active components of Jiedu lotion(Taraxasterol,Matrine)and the hub targets(TGF-?1,TNF-?)have stable binding activity.2.Retrospective clinical study: The results of curative effect evaluation showed that,after fumigation with Jiedu lotion in damp-heat syndrome type LDS patients,CIVIQ score increased,VCSS score decreased,the levels of TGF-?1,TNF-?,hs-CRP decreased significantly.The Logistic regression analysis showed that,the increases of Serum TGF-?1,TNF-?,hs-CRP were independent risk factors for poor CIVIQ and VCSS in patients with damp-heat syndrome type LDS.3.Clinical randomized controlled study:After treatment,the comparisons between the two groups showed that the improvements of serum TGF-?1 in Venous blood of lower extremity,skin hardness,skin thickness,VCSS,CIVIQ in Jiedu lotion group were better than those in control group(P<0.05).Comparisons intra group showed that the Levels of Serum TGF-?1,hs-CRP,TNF-? in Venous blood of lower extremity,skin temperature,skin hardness,superficial fascia thickness,deep fascia thickness,skin thickness,VCSS,CIVIQ of the two groups were improved after treatment(P<0.05).Conclusion: The pathogenesis of LDS is closely related to inflammatory factors and fibrosis,in addition to skin temperature,skin hardness,skin thickness,superficial fascia thickness,deep fascia thickness,VCSS,CIVIQ and other clinical indicators,TNF-?,TGF-?1,hs-CRP are independent indicators of disease progression.The effective active components of Jiedu lotion have good binding degree with TNF-??TGF-?1 molecules,and Jiedu lotion can effectively down regulate the expressions of TGF-?1?TNF-? and hs-CRP,inhibit inflammation and reduce fibrosis,play a role in the treatment of damp-heat syndrome type LDS.