Mechanism and Experimental Verification of Rhodiola rosea L. for the Treatment of Acute Lung Injury Through Network Pharmacology and Molecular Docking

Abstract

Objective: This article endeavors to dissect the bioactive elements, pharmacological effects, and potential mechanisms of Rhodiola rosea L. (RL) concerning acute lung injury (ALI) using a combined approach of network pharmacology and subsequent in vivo experimental validation. Methods: RL constituents and associated targets were retrieved from the Organchem database and pertinent articles. ALI-related targets were meticulously curated through comprehensive searches of GeneCards, OMIM, and DisGeNET databases. Utilizing Cytoscape 3.8.2 software, an intricate RL-ALI ingredients-targets network diagram was fashioned. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape database and microbiota software to unravel the functional and pathway implications of the identified interactions. AutoDock Vina and PyMOL were used to conduct molecular docking. Subsequently, the ALI rats were established by intraperitoneal injection of lipopolysaccharide (LPS) into Sprague Dawley rats, the potential mechanism for treating ALI was validated by kaempferol. Results: 18 active components of RL for ALI were screened, which were related to 306 targets of RL for ALI. Kaempferol (Kae) was a potential major component of ALI treatment. Molecular docking showed Kae had good binding ability to Epidermal Growth Factor Receptor (EGFR), nonreceptor tyrosine kinase, and serine/threonine kinase 1. In addition, at the animal level, Kae alleviated ALI by inhibiting the production of inflammatory cytokines. Lung tissue sections of the Kae-treated group at different doses showed reduced bleeding and reduced exudation of inflammatory factors compared to the LPS cohort. Compared with the LPS group, the secretion of Interleukin-6, tumor necrosis factor-alpha, and Phosphorylated Epidermal Growth Factor Receptor was significantly decreased in the Kae group, while the content of Phosphorylated Protein Kinase B was increased, and the lung injury was alleviated. Conclusion: Through network pharmacology and experimental verification, we identified Kae as the main active ingredient. Kae may reduce the expression of inflammatory factors and regulate the EGFR-AKT signaling pathway, subsequently exerting therapeutic effects in the treatment of ALI.