网络药理学与分子对接联合实验验证的加味二妙散抗急性痛风性关节炎机制研究OA

AIM:To investigate the therapeutic ef-ficacy and potential mechanisms of modified Er Miao-San(MEMS)in the treatment of Acute Gouty Arthritis(AGA).METHODS:Network pharmacology,molecular docking,and molecular dynamics simula-tions were used to validate the interactions be-tween the active components of MEMS and the tar-gets associated with AGA.An AGA model was estab-lished in rats by injecting 25 mg/kg of monosodium urate(MSU)suspension into the right ankle joint.Treatment efficacy was evaluated by measuring an-kle joint swelling,gait scores,and inflammation in-dices.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of TNF-α,IL-6,IL-1β,IL-17,MDA,SOD,and GSH in AGA rats.Hematoxylin and eosin(HE)staining was per-formed to observe the pathological changes in the ankle joint synovial tissue,and Western blotting(WB)was used to analyze the protein levels of NL-RP3 and STAT3 in the synovial tissue.RESULTS:Net-work pharmacology analysis identified quercetin,β-sitosterol,stigmasterol,and wogonin as the core ac-tive components in MEMS for the treatment of AGA.The key therapeutic targets of MEMS in treat-ing AGA include TNF,STAT3,IL-6,and IL-1β.The core active components exhibited strong binding affinity and stable conformations with these tar-gets.The key targets were predominantly enriched in signaling pathways,including NOD-like receptors,IL-17,and TNF.In vivo experiments demonstrated that MEMS effectively reduced ankle joint swelling,improved gait scores,alleviated synovial cell prolif-eration,neutrophil infiltration,and capillary conges-tion in AGA rats.It also lowered the serum levels of TNF-α,IL-1β,IL-6,IL-17,and MDA,while increasing the levels of SOD and GSH.Furthermore,MEMS downregulated the expression of NLRP3 and STAT3 proteins in the synovial tissue.CONCLUSION:MEMS alleviates inflammation and oxidative stress in AGA rats,exerting anti-inflammatory and antioxidative effects.Its mechanism of action may be associated with the modulation of inflammation factor levels via the inhibition of the STAT3/NLRP3 signaling pathway.