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基于网络药理学预测和分子对接的策略探索人参五味子汤抗哮喘的潜在机制

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Ginseng-Schisandra Chinensis decoction against asthma.

作者信息

Zhou Ting, Li Qingqing, Zhang Kaiyue, Zhang Meng, Li Hui, Wu Wei

机构信息

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.

出版信息

Fitoterapia. 2025 Mar;181:106388. doi: 10.1016/j.fitote.2025.106388. Epub 2025 Jan 9.

DOI:10.1016/j.fitote.2025.106388
PMID:39798886
Abstract

BACKGROUND

Ginseng-Schisandra chinensis (GSC) decoction has shown good efficacy in the treatment of asthma (AS), but its t mechanism in the treatment of asthma is still not fully understood.

PURPOSE

This study aims to elucidate the therapeutic mechanism of GSC for AS by identifying the active components of GSC.

METHODS

The chemical composition of GSC was analyzed using UHPLC-MS/MS. The network pharmacology method combined with TCMSP and GeneCards database was used to identify potential targets and enriched pathways related to AS treatment. Use AutoDock for molecular docking to evaluate the binding affinity of active ingredients to core targets. Finally, the LPS-induced A549 cell inflammation model was used to evaluate the effect of GSC on the release of inflammatory cytokines.

RESULTS

The main components in GSC, including ginsenosides (Rf, Rd, Rg2, Ro, Rg5, Rh1) and lignans (schisandrin A, B, schisandrol A, B, schisandrin ester A) were identified. Network analysis revealed 139 intersection targets and highlighted STAT3, TNF, EGFR, IL1B, and AKT1 as key targets, with the PI3K/AKT signaling pathway as the main pathway. Experimental results showed that GSC significantly reduced the levels of IL-1β, IL-6 and TNF-α in LPS-induced A549 cells (p < 0.01), indicating its powerful anti-inflammatory effect.

CONCLUSION

GSC plays a role in treating asthma by targeting STAT3, TNF, IL-1β and AKT1, regulating the PI3K/AKT signaling pathway and inhibiting the release of inflammatory cytokines. These findings provide a basis for the clinical application of GSC.

摘要

背景

人参五味子汤(GSC)在哮喘(AS)治疗中已显示出良好疗效,但其治疗哮喘的机制仍未完全明确。

目的

本研究旨在通过鉴定GSC的活性成分来阐明其治疗AS的机制。

方法

采用超高效液相色谱-串联质谱法(UHPLC-MS/MS)分析GSC的化学成分。运用网络药理学方法并结合中药系统药理学数据库与分析平台(TCMSP)和基因卡片(GeneCards)数据库,鉴定与AS治疗相关的潜在靶点和富集通路。使用自动对接(AutoDock)进行分子对接,以评估活性成分与核心靶点的结合亲和力。最后,利用脂多糖(LPS)诱导的A549细胞炎症模型评估GSC对炎症细胞因子释放的影响。

结果

鉴定出GSC中的主要成分,包括人参皂苷(Rf、Rd、Rg2、Ro、Rg5、Rh1)和木脂素(五味子醇甲、乙,五味子酯甲、乙,五味子酯A)。网络分析揭示了139个交集靶点,并突出显示信号转导和转录激活因子3(STAT3)、肿瘤坏死因子(TNF)、表皮生长因子受体(EGFR)、白细胞介素1β(IL1B)和蛋白激酶B1(AKT1)为关键靶点,以磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路为主要通路。实验结果表明,GSC显著降低了LPS诱导的A549细胞中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平(p < 0.01),表明其具有强大的抗炎作用。

结论

GSC通过靶向STAT3、TNF、IL-1β和AKT1,调节PI3K/AKT信号通路并抑制炎症细胞因子的释放,从而在哮喘治疗中发挥作用。这些发现为GSC的临床应用提供了依据。

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