Lang Jirui, Li Li, Chen Shilong, Quan Yunyun, Yi Jing, Zeng Jin, Li Yong, Zhao Junning, Yin Zhujun
West China School of Pharmacy, Sichuan University, Chengdu, China.
Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
Evid Based Complement Alternat Med. 2022 Oct 7;2022:2377692. doi: 10.1155/2022/2377692. eCollection 2022.
BACKGROUND: Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. OBJECTIVES: To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. METHODS: The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-B, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. RESULTS: 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (-)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1, TNF-, and p38. The data from experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-B, and NLRP3 signaling pathways. CONCLUSION: Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-B, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.
背景：痛风是一种由尿酸单钠（MSU）沉积引起的常见晶体相关性关节炎。藏药五味麝香丸（WSP）已被证明具有抗炎、抗高尿酸血症和抗痛风活性。然而，其潜在机制尚不清楚。 目的：通过网络药理学、分子对接和药理学验证，探讨五味麝香丸治疗痛风性关节炎的机制。 方法：通过在BATMAN-TCM和SwissADME中检索和筛选获得WSP的成分和靶点。从公共数据库中获取涉及痛风的靶点。将共同靶点导入STRING构建蛋白质-蛋白质相互作用（PPI）网络。此外，应用Metascape进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，以预测生物学过程和信号通路。进行分子对接以验证关键成分与肿瘤坏死因子（TNF）信号相关蛋白之间的结合关联。基于血清药理学，在MSU诱导的THP-1巨噬细胞中验证WSP预测的抗痛风机制。分别通过酶联免疫吸附测定（ELISA）和定量逆转录聚合酶链反应（qRT-PCR）检测炎症细胞因子水平和信使核糖核酸（mRNA），并通过蛋白质免疫印迹法和免疫荧光染色法测定丝裂原活化蛋白激酶（MAPK）、核因子-κB（NF-κB）和NLR家族含pyrin结构域蛋白3（NLRP3）信号相关蛋白。 结果：在WSP中发现了48种生物活性成分和165个共同靶点。数据显示，5-顺式-环十五碳烯-1-酮、5-顺式-环十四碳烯-1-酮、（-）-异细辛酮等为潜在活性成分。TNF信号通路、缺氧诱导因子-1（HIF-1）信号通路和Jak-STAT信号通路被预测为抗痛风的潜在通路。分子对接分析发现，大多数成分对p65、NLRP3、白细胞介素-1（IL-1）、TNF-α和p38具有高亲和力。实验数据表明，WSP抑制炎症细胞因子的产生和基因表达。此外，WSP可抑制MAPK、NF-κB和NLRP3信号通路的激活。 结论：我们的研究结果表明，WSP的抗痛风作用可能是通过抑制MAPK、NF-κB和NLRP
Evid Based Complement Alternat Med. 2022-10-7
Front Pharmacol. 2023-8-11
BMC Musculoskelet Disord. 2024-12-20
Front Pharmacol. 2023-8-11
Inflammation. 2021-8
Zotero 插件
