基于网络药理学、分子对接和实验验证探讨金铁锁三萜对类风湿性关节炎的作用机制OA

Objective:Psammosilene tunicoides,a specialty medicine of the Miao ethnic group,is known for its anti-inflammatory and analgesic properties.Despite its recognized benefits,the specific mechanisms through which it influ-ences rheumatoid arthritis are not yet fully understood.Therefore,his study aimed to investigate the therapeutic mecha-nisms of triterpene compounds of Psammosilene tunicoides(TCPT)on rheumatoid arthritis(RA).Methods:Network pharmacology was used to screen key targets and signaling pathways of TCPT in RA,followed by molecular docking to as-sess interactions between active ingredients and these targets.A collagen-induced RA model was utilized,then,arthritis index(AI)score,foot swelling rate,ELISA,histopathological examination(HE),Safranin O,TRAP staining,immunohis-tochemistry,and Western blot were used to validate effects and mechanism.Results:By network pharmacology,seven TCPT active ingredients,such as gypsogenin and epigypsogenin,and 149 drug-disease common targets were obtained.The core targets were TNF,AKT1,PTGS2,etc.The GO analysis involved 498 entries for biological processes,88 entries for cellular components,and 133 entries for molecular functions.KEGG analysis involved 153 signaling pathways,and the top 5 entries were endocrine resistance,the AGE-RAGE pathway in diabetic complications,the Fc epsilon R pathway of IgE,proteoglycan in cancer,and the prolactin signaling pathway.Molecular docking affirmed strong binding affinity be-tween TCPT's active ingredients and core targets.Animal experiments confirmed that compared with the model group,AI and foot swelling rate were reduced in all doses of TCPT treatment groups(P<0.01),the serum RF was reduced(P<0.05),and the levels of TNF-α and IL-6 in ankle cartilage were decreased(P<0.05).HE,Safranin O,and TRAP stai-ning results showed that the pathological changes of the ankle joint were improved.The protein expression levels of MAPK1,MAPK3,MAPK8,MAPK9,and MAPK14,the phosphorylation protein expression of NF-κB P65,and AP-1 and BCL-2 were down-regulated,while expression levels of BAX and Caspase-3 protein were up-regulated(P<0.01 or P<0.05).Conclusion:TCPT exerts therapeutic effects in RA by reducing RF and pro-inflammatory cytokines,inhibiting key phosphorylation events,and modulating apoptotic factors,thereby attenuating ankle cartilage inflammation in CIA mice.