Mechanism Of Caper Fruit Extracts On Of The Fruit Of Capparis Spinosa L. Rheumatoid Arthritis Based On Network Pharmacology And Molecular Docking

Capparis spinosa L.is a traditional Chinese herbal medicine with a wide range of medicinal and economic value.It has been used in Xinjiang folk to treat rheumatoid arthritis,gout,frozen shoulder and other diseases.Modern research showed that the fruit of Capparis spinosa L.contained flavonoids,alkaloids,phenolic acids and volatile oils and other chemical components,which showed anti-inflammatory,analgesic,antibacterial,antioxidant,liver protection,hypoglycemic and hypolipidemic effects.Rheumatoid arthritis is a systemic autoimmune disease,mainly manifested as erosive,multiple,chronic and systemic.In the previous research of the research group,animal experiments have confirmed that the n-butanol extract of the fruit of Capparis spinosa L.has anti-inflammatory,analgesic and anti-rheumatoid arthritis effects,but the specific mechanism action of anti-rheumatoid arthritis are still unclear.On the basis of the above research,based on the network pharmacology and molecular docking,this manuscript studies the mechanism of action of n-butanol extracts of the fruit of Capparis spinosa L.against rheumatoid arthritis,and provides reference and science for the research and development of innovative drugs of the fruit of Capparis spinosa L..(1)In this paper,Capparis spinosa L.is used as the research material.The dried Capparis spinosa L.fruits were arranged the steps of alcohol extraction,rotary evaporation and drying to obtain the n-butanol extracts of the fruit of Capparis spinosa L.,and then the liquid chromatography-mass spectrometry(LC-MS)was used to analyze the extracts,and the silica gel column was used to separate the extracts,and finally the monomer compound 2-methyl-4-pyrone-3-O-rutin glycoside was obtained.(2)Combining the LC-MS analysis results obtained in the previous stage with the Ya TCM database,a total of 80 active ingredients were obtained.The main ingredients include quercetin,luteolin isorhamnetin,etc.The active ingredients were combined with the DTT database for screening.Obtained 262 key targets for the treatment of rheumatoid arthritis,including MMP-1,MMP-9,MMP-13,MAPK14,AKT1,PTGS2,etc.;then we carried out GO analysis,and finally 1099 biological processes were obtained,16 cellular components,133 molecular functions,and KEGG pathway enrichment pathway analysis get 78 pathways enriched by KEGG.The target protein-target protein,active ingredient-target-GO pathway,and active ingredient-target-KEGG pathway were constructed to illustrate how the active ingredients of capers work.(3)Appropriate active ingredients and target proteins were screened out according to the network pharmacology,and the network pharmacology was theoretically verified by molecular docking.The three active components quercetin,luteolin and isorhamnetin were screened out for molecular docking with the target proteins AKT1,PTGS2,MMP-9 and MAPK14;quercetin,luteolin and isorhamnetin were found.It has good binding activity to key targets such as AKT1,PTGS2,MMP-9and MAPK14,among which the active ingredient has the lowest score with MMP-9,and it has a strong binding activity less than-7.0kcal/mol.Active ingredients in n-butanol extract may relieve rheumatoid arthritis by modulating targets.(4)MH7A cells belong to a mature cell line in rheumatoid arthritis fibroblasts,which is a recognized in vitro cell model for the study of RA.The effect of different concentrations of caper n-butanol extracts on the migration ability of MH7 A cells was detected by scratch test.The experiment found that the fruit of Capparis spinosa L.n-butanol extracts it can inhibit the migration of MH7 A cells,and Western blot was used to detect the effect of n-butanol extracts of the fruit of Capparis spinosa L.on the expression of MMP-1,MMP-9,MMP-13 and P-JNK,P-STAT3 signaling pathway proteins.Experiments found that the n-butanol extract of the fruit of Capparis spinosa L.can negatively regulate the expression of P-JNK and P-STAT3 signaling pathways,and inhibit the expression of MMP-1,MMP-9and MMP-13 proteins,which has a certain effect on relieving rheumatoid arthritis.