Clinical Observation And Network Pharmacological Study Of Runzao Decoction In Treating Primary Sjogren’s Syndrome With Qi Deficiency And Jin Deficiency

Primary Sjogren’s syndrome(pSS)is a refractory autoimmune disease,its etiology and pathogenesis remain unclear,and there is currently no effective radical cure.This paper mainly studied the clinical efficacy and safety of Runzao Decoction in the treatment of primary Sjogren’s syndrome with Qi deficiency and Jin deficiency,and discussed the potential active ingredients,targets and mechanism of Runzao Decoction in pSS through the method of network pharmacology.The full text is divided into three parts.Part Ⅰ:literature reviewThis part mainly including the research progress of traditional Chinese medicine and western medicine on primary Sjogren’s syndrome,introduced the understanding of the etiology and pathogenesis of primary Sjogren’s syndrome in traditional Chinese medicine and drug and non-drug therapy,as well as the research of the pathogenesis,clinical manifestations and treatment of primary Sjogren’s syndrome in western medicine.Part Ⅱ:Clinical studiesObjective:To observe the efficacy and safety of Runzao Decoction in treating primary Sjogren’s syndrome with Qi deficiency and Jin deficiency.Methods:50 patients with primary Sjogren’s syndrome with Qi deficiency and Jin deficiency were treated with Runzao Yin decoction,1 dose a day,twice a day,took 12 weeks as a period of treatment.The primary outcome indexes were ESSDAI score and ESSPRI score,and the secondary outcome indexes were TCM syndrome score,exocrine gland function index(Schirmer I test,natural flow rate of saliva test,ocular surface comprehensive analysis,sugar test),inflammation and immune indexes(ESR,IgA,IgG,IgM,C3,C4).Adverse reactions were observed during the treatment.Results:(1)ESSDAI score and ESSPRI score showed statistically significant differences before and after a period of treatment(P<0.05).(2)Efficacy of TCM syndromes:The total effective rate of TCM syndromes after a period of treatment was 77.78%,and the total scores of TCM syndromes,scores of TCM main symptoms and scores of TCM minor symptoms were statistically significant after a period of treatment(P<0.05).(3)Exocrine gland function:tear secretion:there was a statistically significant difference in the left eye and the right eye of patients undergoing Schirmer I test before and after a period of treatment(P<0.05).For patients undergoing comprehensive eye surface analysis,there were statistically significant differences in the tear meniscus height in the left eye before and after a period of treatment(P<0.05),and there was no statistically significant difference in the tear meniscus height in the right eye and in the tear film breakage time in the left eye and the right eye before and after a period of treatment.Salivary secretion:there was a statistically significant difference in the amount before and after a period of treatment of patients with natural salivary flow rate(P<0.05).The difference in the time before and after a period of treatment was statistically significant among patients undergoing the sugar test(P<0.05).(4)Inflammation and immune indexes:there was a statistically significant difference in IgG index before and after treatment(P<0.05),while there were no statistically significant differences in other inflammation and immune indexes before and after treatment.(5)Safety indicators:The vital signs of the patients were stable before and after a period of treatment,with no obvious adverse reactions.Conclusion:Runzao Decoction can reduce the degree of disease activity in patients with primary Sjogren’s syndrome,relieve symptoms such as dryness,fatigue and joint pain,improve the secretion function of lacrimal glands and salivary glands,and regulate the levels of immune indexes.No obvious adverse reactions were found during the treatment,and the safety was good.Part Ⅲ:Network pharmacology studiesObjective:To explore the effective components and mechanism of Runzao Decoction in the treatment of primary Sjogren’s syndrome by network pharmacology.Methods:Collect the chemical composition information and action targets of drugs in Runzao Decoction by searching TCMSP database(screening conditions were OB≥30%,DL≥0.18).Search TTD、OMIM、Drugbank and Genecards databases to obtain the disease targets of primary Sjogren’s syndrome.Cytoscape software was used to construct the network of "TCM-active ingredient-disease target",and 10 key targets and 10 important TCM components were screened out.Use Metascape database to proceed GO enrichment analysis and KEGG pathway analysis(both sCreening conditions were Pvalue<0.05).Results:A total of 172 active ingredients of Runzao Decoction were found to act on 90 disease gene targets of primary Sjogren’s syndrome.Ten core disease targets were screened out as STAT3,JUN,TNF,AKT1,MAPK1,TP53,IL6,CXCL8,MAPK8,ESRl,and 10 important components were kaempferol,luteolin,quercetin,naringin,beta-sitosterol,baicalein,formononetin,licochalconeA,nobiletin,and glycitein.GO enrichment analysis showed that the gene targets of Runzao Decoction for the treatment of primary Sjogren’s syndrome involved 1787 biological processes,92 molecular functions and 70 cellular components.KEGG pathway analysis showed that Runzao Decoction may treat primary Sjogren’s syndrome by regulating TNF signaling pathway,Epstein-Barr virus infection signaling pathway,Th1 cell subgroup signaling pathway,Th17 cell subgroup signaling pathway,IL-17 signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,NF-κB signaling pathway,Thl and Th2 cell differentiation signaling pathway,B cell receptor signaling pathway,etc.Conclusion:Through network pharmacological research methods,it was found that the main active ingredients of Runzao Decoction may act on the gene targets of primary Sjogren’s syndrome,such as STAT3,JUN,TNF,AKT1,MAPK1,TP53,IL6,CXCL8,MAPK8,ESR1,etc.Primary Sjogren’s syndrome may treated by TNF signaling pathway,Epstein-Barr virus infection signaling pathway,Th1 cell subsets signaling pathway,Th17 cell subsets signaling pathway,IL-17 signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,NF-Kappa B signaling pathway,Thl and Th2 cell differentiation signaling pathway,and B cell receptor signaling pathway.