| Part I: Network pharmacologyObjective: Jia Wei Bi Qing Yin’s active compounds,targets,and signaling pathways should be examined in order to treat rheumatoid arthritis(RA),and using network pharmacology techniques,preliminary predictions should be made.Methods: The TCMSP database was searched to find all of the Chinese herbal medications in the formula.The active ingredients and corresponding targets of each medication in the formula were then gathered,and duplicate targets were weeded out to obtain all of the targets that correspond to the formula.The intersection of drug targets and disease-related targets led to the identification of potential targets for RA,which were then subjected to PPI network analysis,GO function analysis,and KEGG signal pathway analysis.The potential targets were subjected to PPI network analysis,GO function analysis,and KEGG signal pathway analysis,which were all visualized and analyzed.Results: 1.The main active ingredients of Jia Wei Bi Qing Yin are quercetin,kaempferol and luteolin,etc.2.The targets shared by RA and Jia Wei Bi Qing Yin total 62.The main targets include TNF,IL-6,IL-1B and STAT3,etc.3.It is predicted that Jia Wei Bi Qing Yin may treat RA by taking part in the JAK/STAT signaling pathway,NF-kappa B signaling pathway,TNF signaling pathway,Th17 cell differentiation,and IL-17 signaling pathway.Conclusions: This study found that the targets and signaling pathways of Jia Wei Bi Qing Yin for the treatment of RA are closely related to the inflammatory response,and predicted that Jia Wei Bi Qing Yin exerts anti-inflammatory effects and alleviates RA via a model with several components,multiple targets,and multiple pathways.Part II: Clinical studyObjective: Jia Wei Bi Qing Yin’s clinical therapeutic impact will be used to assess the herb’s clinical efficacy and safety in people with active rheumatoid arthritis(Shi Re Zu Bi type).Methods: 1.Subjects: A total of 60 RA patients who visited the outpatient and inpatient clinics of the Department of Rheumatology and Immunology of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2020 and December 2021 were randomly assigned to a treatment group and a control group,with 30 cases in each group.2.Treatment regimen: Methotrexate and folic acid were administered to the control group,while Jia Wei Bi Qing Yin was added to the treatment group in addition to the control group.Before and after the course of treatment,the clinical efficacy was compared.3.Efficacy observation: Evaluation of TCM efficacy,DAS28,VAS,TCM evidence score,HAQ,ESR,CRP,RF,anti-CCP antibody index and adverse drug reactions before and after treatment in the two groups.Results: 1.The two patient groups’ data were compared prior to therapy,and there was no statistically significant difference(P > 0.05)between them.2.Comparison of DAS28,VAS,HAQ and TCM evidence points: the fundamental scores were noticeably lower following therapy than they were before to treatment(P <0.05);after treatment,the DAS28,VAS ratings or TCM evidence points in the treatment group were considerably lower than those in the control group(P < 0.05),but there was no difference in the HAQ(P > 0.05).3.Comparison of ESR,CRP,RF and anti-CCP antibody indices: the indices of both groups decreased after treatment compared with those before treatment,and there was a statistical difference(P < 0.05);ESR,CRP and RF indices decreased significantly better than those of the control group after treatment(P < 0.05),while there was no statistical difference in anti-CCP antibody(P > 0.05).4.Comparison of TCM efficacy evaluation: There were significant differences(P <0.05)between the two groups,with the treatment group’s total effective rate(93.33%)being significantly higher than the control group’s(80.00%).5.Comparison of adverse reactions: The rate of adverse events in the treatment group(3.33%)and the rate in the control group(10%)were not significantly different(P > 0.05).Conclusions: 1.The combination of Jia Wei Bi Qing Yin and methotrexate has a stronger effect on relieving the activity of RA than the treatment effect of western medicine alone,indicating that Jia Wei Bi Qing Yin has a better efficacy in treating the active stage of Shi Re Zu Bi type RA.It can fast improve the patient’s quality of life and clinical symptoms while also considerably raising the DAS28,VAS or TCM evidence points,ESR,CRP,and RF indexes.2.The combination of Jia Wei Bi Qing Yin with methotrexate did not increase the occurrence of adverse events and has an effective safety record and should be promoted in clinical settings.Part III: Experimental studyObjective: To investigate the mechanism of the effect of Jia Wei Bi Qing Yin on active Shi Re Zu Bi type RA based on the JAK/STAT signaling pathway.Methods: 1.Peripheral blood of RA patients was used as the study object.Peripheral blood was collected from patients in the treatment and control groups before and after treatment,and the changes of IL-6,IFN-γ,IL-17 cytokine levels and the ratio of Th1 and Th17 cells before and after treatment were detected by ELISA and flow cytology techniques.2.Wistar male rats were used as the study subjects.The normal group consisted of 30 Wistar male rats,while the collagen-induced arthritis(CIA)model was created using the 20 remaining animals.After successful modelling,one group was treated with saline and the other group was treated with Jia Wei Bi Qing Yin,and the rats were executed after28 days of gavage.The expression of p-JAK2,JAK2,p-STAT3 and STAT3 in the synovial tissues was measured by Western blot technique.Results: 1.Comparison of inflammatory indexes in peripheral blood of RA patients:compared with before treatment,the proportions of Th1 and Th17 cells and cytokines IL-6,IFN-γ and IL-17 were significantly lower in peripheral blood after treatment(P <0.05).Following treatment,there was a statistically significant difference(P < 0.05)between the treated group and the control group in terms of the proportion of Th17 cells and the cytokines IL-6,IFN-,and IL-17,although the difference in Th1 was not statistically significant(P > 0.05).2.Protein expression in rat ankle synovial tissue: JAK2,STAT3,and p-JAK2 protein expression were all significantly greater in the CIA group as compared to the control group(P < 0.05);the treatment group’s p-JAK2 and p-STAT3 protein expression was considerably lower than that of the CIA group(P < 0.05),while JAK2 and STAT3 protein expression did not differ significantly from that of the CIA group(P > 0.05).Conclusions:1.Jia Wei Bi Qing Yin can reduce the levels of IL-6,IFN-γ and IL-17 in serum and suppress the expression of Th17 cells,showing that it can inhibit the expression of inflammatory mediators and has potential anti effects,which provides a foundation for the treatment of RA.2.It has been proved by animal experiments that Jia Wei Bi Qing Yin reduces the phosphorylation of JAK2 and STAT3 protein in synovium and inhibits the activation of JAK/STAT3 signaling pathway,which provides a therapeutic strategy for RA... |
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