Liao Xiao-Zhong, Xie Rui-Xia, Zheng Song-Yuan, Fan Cui-Ling, Zuo Meng-Yue, Chen Shi-Xian, Zhu Jun-Qing, Li Juan
Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, PR China.
Phytomedicine. 2025 Jan;136:156257. doi: 10.1016/j.phymed.2024.156257. Epub 2024 Nov 26.
Gout is a common type of arthritis marked by monosodium urate (MSU) crystal deposition in joints, triggering an inflammatory response. Qu-Shi-Xie-Zhuo (QSXZ), a traditional Chinese medicine (TCM) formula, has been clinically used for the treatment of gouty arthritis (GA).
The study sought to examine the impact of QSXZ on GA and to delve into the pharmacological mechanisms that underlie its effects.
The chemical constituents of QSXZ were analyzed through UPLC-MS. MSU-induced acute gouty arthritis (AGA) and subcutaneous (SC) air pouch models in mice were employed to evaluate the anti-inflammatory properties of QSXZ and its primary active compound, Cryptotanshinone (CTS). To investigate the therapeutic mechanisms of QSXZ, we used MS-based network pharmacology, transcriptomic analysis, molecular docking and multiscale bioassays.
Treatment of QSXZ revealed a significant reduction of inflammatory cell infiltration and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin -1β (IL-1β). Based on UPLC/MS/MS results, 49 components were considered the active ingredients of QSXZ. Network pharmacology analysis indicated that QSXZ regulates multiple inflammation-related pathways. Subsequent transcriptomic analysis showed that QSXZ regulates gene expression of S100A8 and S100A9. Our investigation observed an increased expression of S100A8 and S100A9 in monocytes derived from gout patients. Molecular docking and molecular dynamics simulation analysis revealed the binding pattern and interaction between QSXZ active compound CTS and S100A8/A9, and subsequent surface plasmon resonance (SPR) and cell thermal shift assay (CETSA) experiments verified the direct interaction between them. To investigate the mechanisms of action, we conducted RT-PCR, Western blotting, immunohistochemistry, flow cytometry, and measured the inflammatory response. Our findings highlight the pathogenic role of S100A8/A9 mediated TLR4-NLRP3 axis in gout and review outstanding therapeutic effects of QSXZ and its primary active compound CTS on MSU-induced experimental models.
In summary, this study substantiates the therapeutic potential of QSXZ and its primary active compound CTS, as promising alternative treatments for GA. Our findings provide valuable insight into the critical pharmacological mechanism of QSXZ in regulating inflammation, highlighting its potential therapeutic effects in GA management.
痛风是一种常见的关节炎类型，其特征是单钠尿酸盐（MSU）晶体在关节中沉积，引发炎症反应。祛湿泄浊（QSXZ）是一种中药配方，已在临床上用于治疗痛风性关节炎（GA）。
本研究旨在探讨QSXZ对GA的影响，并深入研究其作用的药理机制。
通过超高效液相色谱-质谱联用（UPLC-MS）分析QSXZ的化学成分。采用MSU诱导的小鼠急性痛风性关节炎（AGA）和皮下（SC）气囊模型，评估QSXZ及其主要活性成分隐丹参酮（CTS）的抗炎特性。为了研究QSXZ的治疗机制，我们使用了基于质谱的网络药理学、转录组分析、分子对接和多尺度生物测定法。
QSXZ治疗显著减少了炎症细胞浸润以及促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。基于UPLC/MS/MS结果，49种成分被认为是QSXZ的活性成分。网络药理学分析表明，QSXZ调节多种炎症相关途径。随后的转录组分析表明，QSXZ调节S100A8和S100A9的基因表达。我们的研究观察到痛风患者来源的单核细胞中S100A8和S100A9的表达增加。分子对接和分子动力学模拟分析揭示了QSXZ活性成分CTS与S100A8/A9之间的结合模式和相互作用，随后的表面等离子体共振（SPR）和细胞热位移分析（CETSA）实验验证了它们之间的直接相互作用。为了研究作用机制，我们进行了逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹、免疫组织化学、流式细胞术，并测量了炎症反应。我们的研究结果突出了S
