Zhao Xiangpei, Long Zhaoyang, Zhong Hua, Lu Rongping, Wei Juan, Li Fengzhen, Sun Zongxi
International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, No. 8 Qiuyue Road, Wuxiang New District, Nanning 530201, Guangxi, China.
ACS Omega. 2024 Jul 31;9(32):34303-34313. doi: 10.1021/acsomega.4c00056. eCollection 2024 Aug 13.
To examine the anti-inflammatory properties and underlying mechanisms of Tongfeng Li'an Granules (TFLA), a traditional medicine, in acute gouty arthritis using a rat model.
We identified 55 major compounds in TFLA via ultrahigh-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UPLC-TQF-MS/MS). Databases were employed for the prediction of potential targets, followed by PPI network construction as well as GO and KEGG analyses. After network-pharmacology-based analysis, a rat gouty arthritis model was used to validate the anti-inflammatory mechanism of TFLA.
UPLC-TQF-MS/MS and network pharmacology analyses revealed 55 active ingredients and 160 targets of TFLA associated with gouty arthritis, forming an ingredient-target-disease network. The PPI network identified 20 core targets, including TLR2, TLR4, IL6, NFκB, etc. Functional enrichment analyses highlighted the Toll-like receptor signaling pathway as significantly enriched by multiple targets, validated in in vivo experiments. Animal experiments demonstrated that TFLA improved pathological changes in gouty joint synovium, with decreased ankle joint circumference, serum IL6, IL10, and TNFα levels, as well as reduced protein and mRNA expression of NLRP3, TLR2, and TLR4 in ankle joint synovial tissue observed in the middle- and high-dose TFLA and positive control groups compared to the model group ( < 0.05).
This research elucidated the pharmacological mechanisms of TFLA against gouty arthritis, implicating various ingredients, targets, and signaling pathways. Animal experiments confirmed TFLA's efficacy in alleviating inflammation in acute gouty arthritis by modulating Toll-like receptor signaling and NLRP3 expression.
利用大鼠模型研究传统药物痛风立安颗粒(TFLA)在急性痛风性关节炎中的抗炎特性及潜在机制。
通过超高效液相色谱-四极杆飞行时间质谱联用仪(UPLC-TQF-MS/MS)鉴定TFLA中的55种主要化合物。利用数据库预测潜在靶点,随后构建蛋白质-蛋白质相互作用(PPI)网络并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析。基于网络药理学分析后,使用大鼠痛风性关节炎模型验证TFLA的抗炎机制。
UPLC-TQF-MS/MS和网络药理学分析揭示了TFLA与痛风性关节炎相关的55种活性成分和160个靶点,形成了成分-靶点-疾病网络。PPI网络确定了20个核心靶点,包括Toll样受体2(TLR2)、Toll样受体4(TLR4)、白细胞介素6(IL6)、核因子κB(NFκB)等。功能富集分析突出显示Toll样受体信号通路被多个靶点显著富集,并在体内实验中得到验证。动物实验表明,TFLA改善了痛风性关节滑膜的病理变化,中、高剂量TFLA组和阳性对照组与模型组相比,踝关节周长减小,血清IL6、IL10和肿瘤坏死因子α(TNFα)水平降低,踝关节滑膜组织中NLRP3、TLR2和TLR4的蛋白质和mRNA表达减少(P<0.05)。
本研究阐明了TFLA抗痛风性关节炎的药理机制,涉及多种成分、靶点和信号通路。动物实验证实TFLA通过调节Toll样受体信号和NLRP3表达减轻急性痛风性关节炎炎症的疗效。