What question did this study set out to answer?

This research aims to uncover the therapeutic mechanisms of ligustilide in treating acute lung injury through network pharmacology and laboratory validation.

March 24, 2026Open Access

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

Key Points

This research aims to uncover the therapeutic mechanisms of ligustilide in treating acute lung injury through network pharmacology and laboratory validation.
Combined network pharmacology analysis and in vitro experiments
Screened 227 overlapping targets from public databases
Analyzed protein-protein interaction networks to identify core targets
Conducted pathway enrichment analysis for KEGG pathways
Performed molecular docking to assess binding affinity of ligustilide to PIK3R1
Identified PIK3R1 as a core target within the PPI network
Highlighted the PI3K/Akt/mTOR signaling pathway as significantly enriched
LPS exposure suppressed autophagy and increased inflammatory markers in cell culture
Ligustilide treatment reversed LPS effects by modulating autophagy and reducing inflammatory cytokines
Co-treatment with anti-IL-17 A antibodies further enhanced ligustilide's protective effects through the PI3K/Akt/mTOR pathway

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.

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