Exploring the mechanisms of Huangqin Qingfei Decoction on acute lung injury by LC-MS combined network pharmacology analysis.

ABSTRACT

BACKGROUND: Acute lung injury (ALI) is a respiratory disease characterized by pulmonary inflammation and increased microvascular permeability, resulting in significant mortality and a lack of effective pharmacological treatment. Huangqin Qingfei Decoction (HQQFD), a Traditional Chinese Medicine (TCM) prescription known for its heat-clearing and detoxifying properties, has shown efficacy in treating ALI. However, the underlying mechanisms of HQQFD to against ALI remain to be elucidated. PURPOSE: This study aims to discover the mechanisms and the principal bioactive compounds contributing to HQQFD's protective effects in the treatment of ALI. METHODS: An ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS) method was employed to characterize the chemical profile in HQQFD and xenobiotics (prototypes and metabolites) in rat lung tissue. Based on prototypes identified, a symptom-guided pharmacological networks of ALI were performed. Molecular docking and extensive literature reviews were conducted to validate our findings. RESULTS: A total of 105 compounds were identified in HQQFD, and a total of 194 HQQFD-related xenobiotics (30 prototypes and 163 metabolites) were detected in rat lung tissue. Based on prototypes identified in rat lung, a symptom-guided pharmacological networks of ALI were constructed, AKT1, TNF, EGFR, MMP2, GSK3B, STAT3, MAPK8, IL-6, CDK2 and TP53 were finally identified as key targets. Subsequently, 11 compounds with protective and therapeutic activity were selected by molecular docking analysis, including genipin 1-gentiobioside, chrysin-6-C-α-L-arabinoside-8-C-ß-d-glucoside, scutellarin, chrysin-6-C-ß-d-glucoside-8-C-α-L-arabinoside, 6''-O-[(E)-p-coumaroyl] genipin-gentiobioside, apigenin 7-O-glucoside, baicalin, dihydrobaicalin, wogonoside, crocin I, crocetin. Bioinformatics and literature analysis suggested that, baicalin, wogonoside, genipin 1-gentiobioside and crocetin may be the primary active compounds of HQQFD, potentially targeting GSK3B, MAPK8, IL-6, AKT1 and TNF for HQQFD in addressing ALI. The therapeutic effects of HQQFD may be mediated through the IL-17 and PI3K-AKT signaling pathways. CONCLUSION: The predominant components of HQQFD against ALI are baicalein, wogonoside, genipin 1-gentiobiosid and crocetin, with the IL-17 and PI3K-AKT pathways playing crucial roles. This study provides a foundational guide for future research and introduces innovative methods for exploring the mechanisms of other drug combinations or TCM formulas.