Affiliation:
1. Department of Critical Care Medicine Medical Center of Anesthesiology and Pain The First Affiliated Hospital Jiangxi Medical College Nanchang University Nanchang 330000 China
2. Key Laboratory of Critical Care Medicine Jiangxi Provincial Health Commission Nanchang 330000 China
3. Nanchang Key Laboratory of Diagnosis of Infectious Diseases of Nanchang University Nanchang 330096 China
4. Department of Ophthalmology Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Nanchang 330006 China
5. Department of Critical Care Medicine Nanchang Hongdu Hospital of Traditional Chinese Medicine Nanchang Nanchang 330000 China
Abstract
AbstractAcute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune‐boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro‐inflammatory cytokines in LPS‐induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF‐κB as key overlapping targets within a protein‐protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs′ therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS‐induced upregulation of HSP90 and NF‐κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi‐target, multi‐pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangxi Province