| Background:Rheumatoid arthritis(RA)is a relatively common autoimmune disease.Its pathogenesis is not clear,which may be related to genetic,infection and environmental factors.RA is characterized by persistent or recurrent synovitis,cartilage absorption,bone destruction and bone fiber maintenance,resulting in joint deformity.In recent years,people pay more and more attention to Zhuang medicine with its unique theoretical system and obvious curative effect,and it has been gradually popularized in clinical practice.The traditional "antidote" prescription of Zhuang medicine for the prevention and treatment of rheumatoid arthritis is Longzuan Tongbi Formula.Clinical and experimental studies have found that Zhuang medicine Longzuan Tongbi Formula can significantly improve the clinical symptoms of RA and regulate the expression of many cytokines.Therefore,it is of great significance to fully explore the advantages of traditional ethnic medicine in China,and to further study the characteristics and relevant mechanisms of Zhuang medicine Longzuan Tongbi Formula in the prevention and treatment of RA.Objective:The CIA rat model was used to evaluate the effectiveness of the traditional Zhuang medicine Longzuan Tongbi Formula in the prevention and treatment of RA,and to explore the mechanism of Zhuang medicine Longzuan Tongbi Formula in the treatment of RA from the perspective of the expression and regulation of inflammatory factors,so as to provide theoretical and experimental basis for clarifying the modern connotation of Zhuang medicine's theory of "toxin deficiency causing all kinds of diseases" and "three ways and two ways".Methods:1.By retrieving PubMed,EMBASE,Cochrane Library,CBM,CNKI and other databases,develop the literature research of Zhuang medicine or Zhuang medicine Longzuan Tongbi Formula combined with other drugs to treat RA,using meta-analysis,to evaluate the effectiveness of Zhuang medicine Longzuan Tongbi Formula in the prevention and treatment of RA.2.The CIA rat model was established and randomly divided into five groups(n=10).They were:MTX group?model group and Zhuang medicine Longzuan Tongbi Formula high?medium and low dose administration group,in which Zhuang medicine Longzuan Tongbi Formula was given by gavage daily for 30 days.Ten SD rats were taken as normal control group.Using the arthritis index(AI)to evaluate the effect of Zhuang medicine Longzuan Tongbi Formula on the inflammatory response of CIA rats,and using HE staining to observe and analyze the effect of Zhuang medicine Longzuan Tongbi Formula on the infiltration of arthritis cells,synovial hyperplasia,bone and cartilage destruction and pannus formation;Micro-CT was used to evaluate the inhibitory effect of Zhuang medicine Longzuan Tongbi Formula on the surface injury of the joint bone in CIA rats,and the influence of Zhuang medicine Longzuan Tongbi Formula on the level of serum cytokines(CK)in CIA rats was analyzed by using Luminex multi factor detection technology;By analyzing the changes of body weight,organ coefficients and histopathological sections,the effects of Zhuang medicine Longzuan Tongbi Formula on the system and organs of CIA rats were evaluated.3.The network pharmacology method was used to screen the prevention and treatment of RA related signal pathway of Zhuang medicine Longzuan Tongbi Formula;Western blot was used to verify the protein expression and phosphorylation level of NF-?B p65,a key factor in NF-?B signal pathway;computer simulation of molecular docking was used to screen the possible active components of Zhuang medicine Longzuan Tongbi Formula regulating the expression of inflammatory factors,targeting at NF-?B key factors.Results:1.Six articles were selected for meta-analysis.The results show that the combined final effect of Zhuang medicine Longzuan Tongbi Formula in the treatment of RA is 2.31,95%CI is(1.41,3.77),Z=3.34,P<0.05;the combined final effect of Zhuang medicine Longzuan Tongbi Formula in the treatment of RA ESR was-8.80,95%CI(-14.11,-3.50),Z=3.25,P<0.05;the combined final effect of Zhuang medicine Longzuan Tongbi Formula in the treatment of RA adverse reactions was 0.59,95%CI(0.26,1.37),Z=1.23,P>0.05.2.Zhuang medicine Longzuan Tongbi Formula can significantly reduce the incidence rate and AI score of RA,improve the inflammatory cell infiltration,synovial hyperplasia,bone and cartilage destruction and pannus formation in CIA rats;reduce the values of BS and BS/BV;increase the expression level of IL-10 and decrease the expression level of IL-1? and IL-17A in serum.In addition,under the experimental conditions of this study,the histopathological section showed that there was no significant effect on liver,kidney and testis.Compared with the normal control group,the body weight increased normally,and the organ coefficients of heart?liver?spleen?lung?kidney and testis had no significant difference.3.Using TCMSP database(OB?30%,DL?0.18),a total of 76 active compounds were screened out from the eight compounds of Zhuang medicine Longzuan Tongbi Formula.A total of 54 RA targets were predicted by UniProt database,including IL-10,IL-6 and MMP-9.The results of go enrichment analysis and KEGG pathway analysis showed that Zhuang medicine Longzuan Tongbi Formula was mainly involved in the biological processes such as toxic substance response,nutrition level response and muscle cell proliferation,and played the role in the treatment of RA by regulating the signal pathways such as PI3K/Akt,T cell receptor and NF-?B.In addition,the study found that the high-dose group of Zhuang medicine Longzuan Tongbi Formula can significantly reduce the expression and phosphorylation level of NF-?B p65 protein in the synovium of CIA rats.The results of molecular docking showed that coptisine and hederagenin,which are small molecules in the composition of Zhuang medicine Longzuan Tongbi Formula,have good binding power with NF-?B p65 and NF-?B inhibitor I?B-?,respectively.It is speculated that coptisine,a small molecule in Zanthoxylum nitidum,and hederagenin,a small molecule in Caulis Spatholobi,may be the active components of Zhuang medicine Longzuan Tongbi Formula,a Zhuang medicine,which regulates NF-?B p65 and I?B-?,the targets of RA immune inflammation.Conclusion:1.Longzuan Tongbi Formula is the classic prescription of Zhuang medicine for the prevention and treatment of rheumatoid arthritis.In clinical application,it has been proved that the treatment of RA with Zhuang medicine Longzuan Tongbi Formula or Zhuang medicine Longzuan Tongbi Formula combined with other drugs is a safe and effective treatment strategy.In order to further standardize and popularize the clinical application of Zhuang medicine Longzuan Tongbi Formula,more systematic clinical and experimental animal effectiveness and safety evaluation research is still needed2.The Zhuang medicine Longzuan Tongbi Formula can effectively and safely improve the swelling of the joint surface of CIA rats,inhibit the infiltration of inflammatory cells,synovium hyperplasia,bone and cartilage damage and pannus formation in the joints of CIA rats,prevent the injury of the bone surface,and give full play to the effect of "regulating deficiency and detoxification,connecting the Dragon Road and fire road" in the treatment of RA.3.Zhuang medicine Longzuan Tongbi Formula can significantly reduce the content of IL-17A,IL-1? and increase the content of IL-10 in serum of CIA rats,and play a role in regulating the immune inflammatory response.4.The Zhuang medicine Longzuan Tongbi Formula may play its immunoregulatory role by regulating nine signal pathways,including NF-?B,PI3K/Akt,HIF-1,Tcell receptor,JAK-STAT,VEGF,MAPK,Th17 cell differentiation,toll like receptor.5.NF-?B p65 may be the molecular target of Zhuang medicine Longzuan Tongbi Formula in regulating NF-?B signal pathway to regulate the immune inflammatory response,and coptisine and hederagenin may be the active components combining NF-?B p65 and I?B-?. |
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