Efficacy Evaluation,Action Mechanism And Pharmacodynamic Material Basis Of Zhuang Medicine Fenghegui Against Rheumatoid Arthritis

Objective: To verify the efficacy evaluation of Zhuang medicine Fenghegui against rheumatoid arthritis,screen its active parts against rheumatoid arthritis,and explore its anti-rheumatoid arthritis mechanism and pharmacodynamic material basis.Methods:(1)Rat rheumatoid arthritis model was established with bovine type II collagen and incomplete Freund’s adjuvant,and the changes of the total extract of Fenghegui on the swelling degree and arthritis index of rheumatoid arthritis model rats were observed.The levels of tumor necrosis factor(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and rheumatoid factor(RF)in the serum of rats were detected,and the synovial membrane was observed.Changes in tissue morphology and pathological tissue verify the effect of Fenghegui in the treatment of rheumatoid arthritis.(2)Continue to establish a rat rheumatoid arthritis model with bovine type II collagen and incomplete Freund’s adjuvant,observe the changes of the foot swelling and arthritis index of the rheumatoid arthritis model rats by various parts of Fenghegui,and detect the large The contents of tumor necrosis factor(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and rheumatoid factor(RF)in serum of mice were observed,and the morphology of synovium was observed.And the changes of pathological tissue,the active parts of Fenghegui against rheumatoid arthritis were screened out.Western blot was used to explore the effect of active parts of Fenghegui on the expression of related inflammatory pathway proteins TLR2,TLR4,NF-κB and Myd88 in synovial tissue of rheumatoid arthritis rats,and to explore the anti-rheumatoid arthritis effect of Fenghegui Mechanisms.(3)By means of liquid chromatography-mass spectrometry,combined with the Fenghegui compound mass spectrometry database and Mass Bank,Chemspider and other databases established by the research group in the early stage,the serum of the rats after oral administration of the ethyl acetate part of Fenghegui was analyzed and identified.Results:(1)Verification of the anti-rheumatoid arthritis effect of Fenghegui:Compared with the model group,the extract of Fenghegui can significantly reduce the degree of foot swelling and arthritis index in CIA rats;it can significantly reduce the inflammation in serum The levels of rat tumor necrosis factor(TNF-α),rat interleukin-6(IL-6),rat interleukin-1β(IL-1β)and rat rheumatoid factor(RF)among factors;The results of the pathological section of the rat synovium showed that the extract of Fenghegui could improve the pathological changes of the synovium of the rats in the model group,slow down the synovial hyperplasia,and reduce the infiltration of inflammatory cells.(2)Screening of active sites and mechanism of action of Fenghegui against rheumatoid arthritis: The experimental results show that compared with the model group,the ethyl acetate of Fenghegui can significantly reduce the degree of foot swelling and arthritis index in CIA rats;Significantly reduced serum inflammatory factors rat tumor necrosis factor(TNF-α),rat interleukin-6(IL-6),rat interleukin-1β(IL-1β)and rat rheumatoid factor(RF)level;the results of rat synovial pathological section showed that the ethyl acetate of maple lotus and cinnamon could improve the pathological changes of the synovial membrane of model rats and reduce the infiltration of inflammatory cells.The experimental results of related inflammatory proteins in synovial tissue showed that,compared with the model group,the Zhuang medicine Fenghegui ethyl acetate high-dose group could significantly reduce the expressions of related inflammatory proteins TLR2,TLR4,NF-κB and Myd88 in synovial tissue.(3)Research on the material basis of anti-rheumatoid arthritis of the active parts of Fenghegui: The experimental results show that: in the negative ion mode,the drug-containing serum of the ethyl acetate parts of Fenghegui was analyzed by oral administration of the rats,and the final identification and speculation were made.The blood components of the ethyl acetate part of Fenghegui: 15 prototype components,of which 8 are flavonoids,6 are stilbene,and 1 phenolic acid;17metabolites,of which 11 are diphenyl Ethylene metabolites,6 of which are flavonoid metabolites.Conclusions:(1)Fenghegui can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis,and the ethyl acetate part of Fenghegui is the active part of Fenghegui against rheumatoid arthritis;(2)Fenghegui Gui can relieve the symptoms of joint inflammation in CIA rats,which is related to the inhibition of the inflammatory response mediated by the TLR4/NF-κB signaling pathway;(3)The potential anti-RA active components in the ethyl acetate part of Fenghegui are: isorhapontin,phloretin,catechin,oxyresveratrol,andalasin A,morin,afzelechin and their metabolites.