A novel mechanism for treating acute lung injury with ligustilide: elucidation via network pharmacology and in vitro validation

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2026-03-21 DOI:10.1007/s11418-026-02011-y

Yi Yu, Zhennan Wang, Chentong Pan, Keyao Zhu, Liying Xu

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引用次数: 0

Abstract

Ligustilide inhibits the release of multiple inflammatory factors and alleviates acute lung injury (ALI), although its underlying mechanisms require further investigation. This study combined network pharmacology and in vitro experiments to systematically elucidate the therapeutic mechanism of ligustilide against lipopolysaccharide (LPS)-induced ALI. Potential targets of ligustilide and ALI-related genes were screened from public databases, identifying 227 overlapping targets. Protein-protein interaction (PPI) network analysis revealed PIK3R1 as core targets. KEGG pathway enrichment analysis highlighted the PI3K/Akt/mTOR signaling axis as one of the most significantly enriched pathway (P < 0.001). Molecular docking confirmed a strong binding affinity between ligustilide and the PIK3R1 protein. In vitro, LPS exposure (10 µg/ml, 48 h) suppressed autophagy in HPAEpiCs, evidenced by reduced Beclin-1 and LC3 protein levels and a decrease in autophagic vesicles, while concurrently activating the PI3K/Akt/mTOR signaling pathway (P < 0.01) and elevating the levels of IL-17 A, IL-6, and TNF-α. Treatment with ligustilide (25 µg/ml) significantly reversed these effects by modulating autophagy-related markers and suppressing the release of these inflammatory cytokines (P < 0.05). Furthermore, co-treatment with anti-IL-17 A neutralizing antibodies amplified these protective effects through enhanced inhibition of the PI3K/Akt/mTOR pathway (P < 0.01). These findings suggest that ligustilide alleviates ALI by modulating autophagy-related markers and inhibiting inflammatory responses via the IL-17 A-mediated PI3K/Akt/mTOR signaling pathway. The integration of network pharmacology with experimental validation provides a robust mechanistic framework for understanding ligustilide’s therapeutic potential against ALI.

Graphical abstract

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藁本内酯治疗急性肺损伤的新机制：网络药理学阐释及体外验证。

藁本内酯抑制多种炎症因子的释放，减轻急性肺损伤（ALI），但其潜在机制有待进一步研究。本研究将网络药理学与体外实验相结合，系统阐明藁本内酯对脂多糖（LPS）诱导的ALI的治疗机制。从公共数据库中筛选藁本内酯和ali相关基因的潜在靶点，鉴定出227个重叠靶点。蛋白-蛋白相互作用（PPI）网络分析显示PIK3R1是核心靶点。KEGG通路富集分析显示PI3K/Akt/mTOR信号轴是最显著富集的通路之一（P < 0.001）。分子对接证实了liguslide与PIK3R1蛋白之间具有很强的结合亲和力。在体外，LPS暴露（10µg/ml, 48 h）抑制HPAEpiCs的自噬，表现为Beclin-1和LC3蛋白水平降低，自噬囊泡减少，同时激活PI3K/Akt/mTOR信号通路（P < 0.01），升高IL-17 a、IL-6和TNF-α水平。用藁本内酯（25µg/ml）通过调节自噬相关标志物和抑制这些炎症细胞因子的释放，显著逆转了这些作用（P < 0.05）。此外，与抗il - 17a中和抗体共同处理，通过增强抑制PI3K/Akt/mTOR通路，增强了这些保护作用（P < 0.01）。这些发现表明，藁本内酯通过IL-17 a介导的PI3K/Akt/mTOR信号通路调节自噬相关标志物，抑制炎症反应，从而减轻ALI。网络药理学与实验验证的结合为理解藁本内酯治疗ALI的潜力提供了一个强大的机制框架。图形抽象此图像的替代文本可能是使用AI生成的。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.

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