| Objective: In order to provide a reference for the development and utilization of Aralia echinocaulis Hand.-Mazz.and Aralia cordata Thund.,compared and analyzed the mechanisms in the treatment of rheumatoid arthritis(RA).Methods:This study used the research method of network pharmacology.Screened the therapeutic targets of A.echinocaulis and A.cordata in the treatment of RA.Searched for key genes in the therapeutic target interaction network,and predicted the potential anti-disease pathway.On this basis,the animal experiment scheme was designed.Rats were used to establish the collagen-induced arthritis model.Used methotrexate as positive control,compered the therapeutic effects of A.echinocaulis and A.cordata on model rats.Metabonomics techniques were used to analyze differential metabolites and related pathways.Through multi-approach and multi-target,the possible mechanism of difference in efficacy of A.echinocaulis and A.cordata in the treatment of RA was explained.Results:(1)The results of network pharmacological analysis show that A.echinocaulis and A.cordata regulate the occurrence of RA through ESR1,ESR2,MAPK8,MAPK1,EGFR and CASP3 targets,IL-17 signal pathway and TNF signal pathway.A.cordata may also be effective in the treatment of RA by affecting osteoclast differentiation and AGE-RAGE signaling pathway in diabetic complications.(2)The results of animal experiments showed that compared with the normal group and model group,A.echinocaulis and A.cordata could significantly reduce joint swelling,arthritis score index,synovial inflammatory cell infiltration and proliferation,and serum TNF-α level in CIA rats.But there was no significant difference in efficacy between A.echinocaulis and A.cordata(P > 0.05).(3)The results of metabonomics analysis showed that there were differential metabolites in rat serum after treatment,which were mainly related to AGE-RAGE signal pathway,PI3K-Akt signal pathway and so on.Conclusion: In terms of composition,related targets and signal pathway,there are differences in the mechanism of anti-RA between A.echinocaulis and A.cordata.They could significantly reduce the symptoms of joint inflammation and synovial tissue infiltration and proliferation in CIA model rats,but the effect was not significant(P >0.05).These differential metabolites play a role in the treatment of RA mainly by affecting AGE-RAGE signal pathway and PI3K-Akt signal pathway. |