Key Target Research In Traditional Chinese Medicine For The Treatment Of Psoriasis-Vitiligo Comorbidity And Real-World Experimental Validation Based On Co-Analysis Of Multi-Omics

Objective(1)To summarise the dosing pattern in the prescription for psoriasis-vitiligo comorbidity and extract the core medicinals.(2)Network pharmacology analysis of core medicinals for psoriasis-vitiligo comorbidity to predict therapeutic targets.(3)Validation of key targets for psoriasis-vitiligo comorbidity through real-world experiments.Methods(1)Retrieve the medical record information of all patients with psoriasis-vitiligo comorbidity hospitalised in the Department of Dermatology from 1 January 2015 to 31 December 2021 in the medical record system of the Tianjin Academy of Chinese Medicine Affiliated Hospital,and analyse the patient’s gender,tongue and pulse,symptoms,and the four properties and five flavors,channel tropism and efficacy of Chinese medicinal using the Formulary Analysis.The module of formula analysis was used to perform association rule analysis to obtain key medicinals and to summarise the core medicinals in conjunction with the network topology map.(2)Use network pharmacology to construct a drug-common target-disease network of core medicinals for the treatment of psoriasis-vitiligo comorbidity,and analyse and mine the main compounds in the core medicinals and the core targets in the regulatory targets.(3)Complete ethical review related to clinical trials,fully inform patients with psoriasis-vitiligo comorbidity of the study specifics and alternative protocols;patients who sign an informed consent form are included in the study;perform general transcriptome sequencing on patients’ skin tissues;perform whole transcriptome sequencing and proteomic studies on patients’ peripheral blood samples before and after treatment,and analyse and validate key targets of psoriasis-vitiligo comorbidity.Results(1)Ten patients with psoriasis-vitiligo comorbidity were included and the statistic results of the tongue manifestation were: "Red tongue with yellowish coating" in 70%,"red tongue with yellowish and greasy coating" in 20%,"dark red tongue with yellow coating" in 10%.The statistic results of pulse were: "Rapid pulse" accounted for 70% of the cases,while "slippery pulse","string-like pulse" and "slippery and rapid pulse" accounted for 10% each.The statistic results of pattern and sign were: "Pattern of blood-heat" accounted for 80% of cases and "pattern of damp-heat" for 20% of cases.Ten prescriptions were chosen,involving52 kinds of medicinals.The four qi are mainly concentrated in coldness,and also in neutral and warm;the five flavors are mainly concentrated in sweet,and also in bitterness and acrid;the channel tropism is mainly concentrated in the lung and stomach meridians,and also in the heart,spleen,liver and kidney meridians.The total frequency of medicinal use was 182 times and the medicinals association analysis screened the key medicinals was: Radix Rehmanniae Recens,Flos Lonicerae,Radix Scrophulariae,Rhizoma Smilacis Glabrae,Fructus Forsythiae,Radix Scutellariae,Fructus Arctii,Semen Ziziphi Spinosae,Radix Glycyrrhizae.The core medicinals are: Radix Rehmanniae Recens,Flos Lonicerae.(2)There are 43 active compounds of the core medicinals Radix Rehmanniae Recens and Flos Lonicerae,which can regulate 292 targets of action,and 163 targets of psoriasis-vitiligo comorbidity;the targets of the core drug compounds and the targets of the comorbidities were intersected,and 28 common targets of action were screened.Building a drug-common target-disease network with quercetin,lignocaine,kaempferol,adenosine and beta-sitosterol playing a major role in the core drug treatment of psoriasis-vitiligo comorbidity,with quercetin modulating the largest number of targets and being the major compound.IFN-γ,HMOX1,PTGS2,ICAM1,TNF and IL-1β are the key targets for the treatment of psoriasis-vitiligo comorbidity by Radix Rehmanniae Recens and Flos Lonicerae,among which IFN-γ can regulate the remaining five key targets for the treatment of psoriasis-vitiligo comorbidity by Radix Rehmanniae Recens and Flos Lonicerae,and IFN-γ is the core drug for the treatment of psoriasis-vitiligo comorbidity.(3)The GSEA algorithm GO functional enrichment of the skin general transcriptome showed increased expression levels of the IFN-γ pathway in psoriasis,vitiligo and the co-morbid states of psoriasis and vitiligo;whole transcriptome sequencing of peripheral blood after treatment compared to peripheral blood before treatment showed that the IFN-γ pathway genes: The m RNA expression of IFN-γ,JAK1,JAK2,STAT1,ISG15 and ISG20 all decreased,with IFN-γ decreasing most significantly,indicating a significant decrease in IFN-γexpression at the gene level after treatment;the proteomic results of peripheral blood after treatment versus before treatment showed a decrease in complement-related proteins in peripheral blood after treatment,and that IFN-γ is a key target for psoriasis-vitiligo comorbidity.Conclusions(1)Patients with psoriasis and vitiligo have a red tongue with yellow coating and a number of heat signs,and a greasy coating and slippery pulse with wet signs.The herbal combination of Radix Rehmanniae Recens and Flos Lonicerae can clear heat and cool the blood,remove wind and toxins,nourish yin and promote the production of body fluid,clearing heat from the blood and relieving the incandescence of heat and toxins.It is the core drug for the treatment of psoriasis-vitiligo comorbidity.(2)Quercetin,lignan and kaempferol in Flos Lonicerae,adenosine in Radix Rehmanniae Recens,and β-sitosterol co-occurring in Flos Lonicerae and Radix Rehmanniae Recens are the compounds that play a major role in the treatment of psoriasis-vitiligo comorbidity by the core medicinals.Among the key targets of raw licorice and goldenseal in the treatment of psoriasis-vitiligo comorbidity,IFN-γ can down-regulate HMOX1,which has a protective effect on psoriasis-vitiligo comorbidity,and up-regulate PTGS2,ICAM1,TNF and IL-1β,which have an exacerbating effect on psoriasis-vitiligo comorbidity,IFN-γ is the core target of the core medicinals in the treatment of psoriasis-vitiligo comorbidity.(3)Patients with psoriasis-vitiligo comorbidity treated with TCM showed good symptom relief.The combined multi-omics analysis of IFN-γ-related genes and protein changes in skin and blood samples before and after treatment showed that TCM may treat psoriasis-vitiligo comorbidity by down-regulating IFN-γ,which is a key target in psoriasis-vitiligo comorbidity.