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基于 LC-LTQ-Orbitrap-MS 与网络药理学分析四君子汤治疗细胞毒性相关卵巢早衰的活性成分及其作用机制

Integration of LC-LTQ-Orbitrap-MS and Network Pharmacology to Analyze the Active Components of Sijunzi Decoction and their Mechanism of Action Against Cytotoxicity-associated Premature Ovarian Insufficiency.

机构信息

The Laboratory of Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, P.R. 210029, China.

No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, P.R. 210029, China.

出版信息

Comb Chem High Throughput Screen. 2023;26(14):2437-2451. doi: 10.2174/1386207326666230303094247.

Abstract

INTRODUCTION

Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI.

METHODS

We identified compounds in SJZD using liquid chromatography-linear trap quadrupole- Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS). Traditional Chinese Medicine Systems (TCMSP) and HERB databases were used to identify the ingredients and potential targets of SJZD. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape3.9.1.

RESULTS

We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive. The screen outputted yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI.

CONCLUSION

Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.

摘要

简介

四君子汤(SJZD)是一种经典的中药方剂,可增强神经免疫内分泌功能,缓解炎症性衰老,这是卵巢早衰(POI)的关键发病机制。然而,SJZD 缓解 POI 的机制尚不清楚。因此,我们旨在确定 SJZD 的活性成分及其治疗 POI 的作用机制。

方法

我们使用液相色谱-线性阱四极杆-Orbitrap 质谱联用仪(LC-LTQ-Orbitrap-MS)鉴定 SJZD 中的化合物。使用中药系统药理学分析平台(TCMSP)和草药数据库鉴定 SJZD 的成分和潜在靶点。我们使用 RStudio 分析基因本体论(GO)术语和京都基因与基因组百科全书(KEGG)途径的富集,并使用 Cytoscape3.9.1 构建可视化网络。

结果

我们使用 LC-LTQ-Orbitrap-MS 鉴定了 98 种化合物,其中 29 种具有生物活性。筛选结果输出了这些化合物与 POI 相关的 151 个预测靶点。GO 和 KEGG 分析的结果表明,这些化合物在细胞生长、分裂、迁移和存活信号通路中发挥关键作用。因此,磷脂酰肌醇 3-激酶(PI3K)/AKT、丝裂原活化蛋白激酶(MAPK)和表皮生长因子受体(EGFR)途径可能与 SJZD 对 POI 病理过程的药理作用密切相关。

结论

我们的研究结果为快速分析 SJZD 的生物活性成分及其药理机制提供了科学依据。

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