■急性痛风性关节炎(AGA)的特征是关节内尿酸单钠晶体的积累,导致炎症和剧烈疼痛。西医治疗在解决这种情况方面具有局限性。以往的研究表明,秦皮通风方(QPTFF)治疗AGA的疗效,但是需要进一步调查以了解其作用机制。
■我们使用超高效液相色谱串联Q-ExactiveOrbitrap高分辨率质谱(UHPLC-Q-Orbitrap-MS)来鉴定QPTFF中的化合物。这些化合物调控的靶蛋白从中药系统药理学数据库和分析平台获得,化学数据库,和瑞士目标预测数据库。从各种数据库中搜索和筛选AGA相关目标,包括基因卡,PharmGKB,药店,等。分析了QPTFF和AGA的相交靶标的蛋白质-蛋白质相互作用网络,GO功能富集,和KEGG途径富集。然后,我们使用AGA大鼠模型验证了QPTFF的作用机制,通过H&E染色评估病理变化,通过ELISA评估靶表达,RT-qPCR,和Westernblot。
■UHPLC-Q-Orbitrap-MS在QPTFF中鉴定出207种化合物,通过网络药理学选出55名。在589个复合调控靶标和1204个AGA相关靶标中,183个潜在靶标与QPTFF治疗AGA有关。主要靶蛋白包括IL-1β,NFKBIA,IL-6,TNF,CXCL8和MMP9,IL-17信号通路主要受QPTFF调控。实验结果表明,中、高剂量QPTFF显著降低血清炎症因子和MMP-9的表达,并抑制IL-17A,IL-6,IKK-β,AGA大鼠NF-κBp65mRNA及蛋白表达与模型组比较。
■QPTFF的关键目标包括IL-1β,NFKBIA,IL-6,TNF-α,CXCL8和MMP9。QPTFF能有效缓解AGA大鼠关节炎症,高剂量表明没有肝或肾毒性。其治疗AGA的抗炎机制涉及IL-17A/NF-κBp65信号通路。
UNASSIGNED: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action.
UNASSIGNED: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein-protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF\'s mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot.
UNASSIGNED: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF\'s treatment of AGA. Main target proteins included IL-1β, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-β, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group.
UNASSIGNED: Key targets of QPTFF include IL-1β, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.