Changchun University of Chinese Medicine, Changchun, Jilin, China.
Rapid Commun Mass Spectrom. 2024 Jan 30;38(2):e9664. doi: 10.1002/rcm.9664.
TongFu XieXia Decoction (TFXXD), a formulation rooted in traditional Chinese medicine and optimized through clinical practice, serves as an advanced version of the classic Da Cheng Qi decoction used for treating intestinal obstruction (IO), demonstrating significant therapeutic efficacy. However, due to the intricate nature of herbal compositions, the principal constituents and potential mechanisms of TFXXD have yet to be clarified. Accordingly, this study seeks to identify the active compounds and molecular targets of TFXXD, as well as to elucidate its anti-IO mechanisms.
Qualitative identification of the principal constituents of TFXXD was accomplished using ultra-high preformance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS/MS) analysis. PharmMapper facilitated the prediction of potential molecular targets, whereas protein-protein interaction analysis was conducted using STRING 11.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Metascape database. A "compounds-target-pathway" network was meticulously constructed within Cytoscape 3.8.2. Finally, molecular docking studies were performed to investigate the interactions between the core target and the crucial compound.
UPLC-Q-Orbitrap-MS/MS analysis identified 65 components with high precision and sensitivity. Furthermore, 64 potential targets were identified as integral to TFXXD bioactivity in IO treatment. Gene Ontology enrichment analysis revealed 995 distinct biological functions, while the Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 143 intricate signaling pathways.
Molecular docking studies substantiated the substantial affinity between the TFXXD bioactive constituents and their corresponding targets in the context of IO. TFXXD exerts its therapeutic efficacy in IO through a multifaceted interplay between multiple compounds, targets, and pathways. The integration of network pharmacology with UPLC-Q-Orbitrap-MS/MS has emerged as a promising strategy to unravel the intricate web of molecular interactions underlying herbal medicine. However, it is imperative to emphasize the necessity for further in vivo and in vitro experiments.
通腑泻下汤（TFXXD）是一种源于中医并经过临床实践优化的配方，是治疗肠梗阻（IO）的经典大承气汤的升级版，具有显著的治疗效果。然而，由于草药成分的复杂性，TFXXD 的主要成分和潜在机制尚未得到阐明。因此，本研究旨在确定 TFXXD 的活性化合物和分子靶点，并阐明其抗 IO 机制。
采用超高效液相色谱-四极杆轨道阱质谱联用（UPLC-Q-Orbitrap-MS/MS）分析对 TFXXD 的主要成分进行定性鉴定。PharmMapper 用于预测潜在的分子靶点，而 STRING 11.0 用于进行蛋白质-蛋白质相互作用分析。使用 Metascape 数据库进行基因本体论和京都基因与基因组百科全书途径富集分析。在 Cytoscape 3.8.2 中精心构建了“化合物-靶标-途径”网络。最后，进行分子对接研究以研究核心靶标与关键化合物之间的相互作用。
UPLC-Q-Orbitrap-MS/MS 分析鉴定了具有高精度和高灵敏度的 65 种成分。此外，鉴定出 64 个潜在靶点是 TFXXD 治疗 IO 的生物活性的关键。基因本体论富集分析揭示了 995 种不同的生物学功能，而京都基因与基因组百科全书富集分析确定了 143 个复杂的信号通路。
分子对接研究证实了 TFXXD 生物活性成分与其在 IO 中的对应靶点之间存在显著的亲和力。TFXXD 通过多种化合物、靶标和途径的相互作用发挥其在 IO 中的治疗作用。网络药理学与 UPLC-Q-Orbitrap-MS/MS 的结合为揭示草药中分子相互作用的复杂网络提供了一种很有前途的策略。但是，必须强调进一步进行体内和体外实验的必要性。
