Chlorogenic acid mitigates acute respiratory distress syndrome via inhibition of the PI3K/AKT signalling pathway: an integrated analysis of bioinformatics and validation experiments.

OBJECTIVE

High mortality rates are linked to acute respiratory distress syndrome (ARDS), a prevalent type of respiratory failure. Amid the COVID-19 outbreak in particular, a viable defensive method is provided by traditional Chinese medicine (TCM). This study investigated whether chlorogenic acid (CGA), a primary component of honeysuckle, could protect against ARDS.

METHODS

We employed network pharmacology to explore the honeysuckle and ARDS component-target-disease network, and enrichment function analysis to uncover the potential mechanisms of honeysuckle in treating ARDS. LPS-induced ARDS rat models (each group rats n = 6) were used for validation, and the CGA treatments group were was administered by gavage at 100 mg/kg. including flow cytometry for T cell subsets, ELISA for inflammatory factors, and neutrophil extracellular trap (NET) markers. Histological, immunofluorescence, and transmission electron microscopy analyses were conducted to evaluate CGA's role of CGA in ARDS. mRNA sequencing and molecular docking and surface plasmon resonance (SPR) analysis were performed to determine CGA's influence on the PI3K/AKT signalling pathway.

RESULTS

We identified 144 common drug-disease targets, with honeysuckle containing 23 potentially active components. Key genes included STAT3, PIK3CA, and AKT1, which are involved in the PI3K/AKT, HIF-1, and Ras signalling pathways. Compared to the control group, in vivo studies revealed a marked diminution by CGA in cellular infiltration, oedema, and interstitial thickness observed in lungs impacted by ARDS. Furthermore, inflammatory mediators like IL-6, IL-1β, TNFα, IL-10 were lowered through CGA administration, alongside NET indicators including PAD4, citH3, and myeloperoxidase (MPO). T cell subtypes were altered during ARDS and CGA intervention. Molecular docking indicated a strong binding of CGA to PI3K and AKT1. SPR analysis further confirmed a high-affinity binding between CGA and PI3K, characterized by a low equilibrium dissociation constant (KD).

CONCLUSION

CGA alleviates ARDS by inhibiting the PI3K/AKT signaling pathway, thereby suppressing inflammation, regulating T-cell subtypes, and reducing NET formation.