Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, PR China.
Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, PR China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118863. doi: 10.1016/j.jep.2024.118863. Epub 2024 Sep 27.
Xiangsha Liujunzi Wan (LJZW) is a traditional Chinese medicine (TCM) formula containing a variety of traditional Chinese herb components. Its principal components are often used in the treatment of gastrointestinal diseases and contribute to the treatment of Crohn's disease (CD).
To explore the therapeutic potential of LJZW in CD through network pharmacology, bioinformatics, molecular docking, and experimental verification.
The principal bioactive components and corresponding targets of LJZW were ascertained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Potential targets for CD were identified in GeneCards, OMIM, DrugBank, DisGeNET, CTD, and Gene Expression Omnibus (GEO) databases. Intersection targets of LJZW and CD were identified using a Venn diagram and visualized using Cytoscape 3.8.0 to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to assess the function of intersection targets. AutoDockTools and PyMOL were used for molecular docking to recognize the association between the core ingredients of LJZW and the core targets of CD. Subsequently, a series of experiments were conducted for validation.
The network pharmacology results indicated that there were 156 bioactive components and 268 corresponding targets for LJZW, 3023 primary relevant targets for CD, and 169 intersection targets for LJZW and CD. The PPI network was employed to identify five hub genes and six clusters. The GO functional analysis indicated that intersection targets are primarily correlated with oxidative stress and inflammatory responses. KEGG pathway analysis revealed that these targets were primarily associated with the phosphotylinosital 3 kinase (PI3K)-protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. The molecular docking results showed that the core ingredients of LJZW had good binding ability with the core targets of CD. A series of experiments demonstrated that LJZW could effectively attenuate TNBS-induced colitis symptoms, inhibit the inflammatory response, and protect intestinal barrier function by inhibiting the PI3K-AKT and MAPK signaling pathways, thus preventing and treating CD.
LJZW has the characteristics of multi-component, multi-target, and multi-pathway treatment, which helps to improve the treatment of CD, protect the intestinal barrier, and exert the effect of anti-inflammatory therapy by inhibiting PI3K-AKT and MAPK signaling pathways.
香砂六君子丸（LJZW）是一种含有多种中药成分的中药方剂。其主要成分常用于治疗胃肠道疾病，并有助于治疗克罗恩病（CD）。
通过网络药理学、生物信息学、分子对接和实验验证，探讨 LJZW 治疗 CD 的治疗潜力。
从中药系统药理学数据库和分析平台（TCMSP）中确定 LJZW 的主要生物活性成分及其相应的靶点。在 GeneCards、OMIM、DrugBank、DisGeNET、CTD 和基因表达综合（GEO）数据库中确定 CD 的潜在靶点。使用 Venn 图确定 LJZW 和 CD 的交集靶点，并使用 Cytoscape 3.8.0 可视化构建蛋白质-蛋白质相互作用（PPI）网络。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析评估交集靶点的功能。使用 AutoDockTools 和 PyMOL 进行分子对接，以识别 LJZW 的核心成分与 CD 的核心靶点之间的关联。随后进行了一系列验证实验。
网络药理学结果表明，LJZW 有 156 种生物活性成分和 268 个相应靶点，CD 有 3023 个主要相关靶点，LJZW 和 CD 有 169 个交集靶点。PPI 网络用于识别五个枢纽基因和六个聚类。GO 功能分析表明，交集靶点主要与氧化应激和炎症反应相关。KEGG 通路分析表明，这些靶点主要与磷酸肌醇 3 激酶（PI3K）-蛋白激酶 B（AKT）和丝裂原活化蛋白激酶（MAPK）信号通路相关。分子对接结果表明，LJZW 的核心成分与 CD 的核心靶点具有良好的结合能力。一系列实验表明，LJZW 通过抑制 PI3K-AKT 和 MAPK 信号通路，有效减轻 TNBS 诱导的结肠炎症状，抑制炎症反应，保护肠道屏障功能，从而预防和治疗 CD。
LJZW 具有多成分、多靶点、多途径治疗的特点，通过抑制 PI3K-AKT 和 MAPK 信号通路，有助于改善 CD 的治疗，保护肠道屏障，发挥抗炎治疗作用。
