Ziyang Zhang (223533), Ziyang Zhang (223533), Tianyi Zhu, Liang Cao, Y. F. Wang, Xiaoliang Xing, Zaiqi Zhang, Zaiqi Zhang
Madeng'ai (MDA) is a traditional medicinal plant of the Dong ethnic group. Its roots have been widely used in folk medicine for clearing heat and removing toxins, alleviating swelling and relieving pain, dispersing blood stasis and arresting bleeding, as well as promoting wound healing. It is taxonomically classified as a variety of Potentilla freyniana Bornm . Acute lung injury (ALI) is a life-threatening pulmonary disorder associated with high mortality, underscoring the urgent need to explore novel therapeutic strategies. This study aimed to evaluate the protective effects of the ethyl acetate fraction of MDA (MEA) against LPS-induced ALI in mice and to investigate its underlying mechanisms. LC-MS/MS was employed to tentatively identify the bioactive components of MEA. A mouse model of ALI was established by LPS induction. The protective effects of MEA were evaluated through assessments of lung histopathology, inflammatory cytokine levels, and oxidative stress markers. The underlying mechanisms were systematically investigated by integrating transcriptomics, metabolomics, network pharmacology, molecular docking, and Western blotting. MEA significantly attenuated LPS-induced pulmonary pathological lesions, pulmonary edema, and excessive inflammatory responses in ALI mice. Comprehensive bioinformatics analyses predicted potential mechanisms involving oxidative stress and the regulation of metabolic pathways. Experimental validation via Western blotting confirmed that MEA inhibited TLR4-mediated inflammatory signaling and modulated the PI3K/AKT pathway, thereby exerting multi-pathway protective effects against ALI. Collectively, this study confirms that MEA, as a traditional herbal extract, holds potential as an adjuvant therapeutic agent for ALI, providing experimental evidence for the modernization and development of ethnic medicines. • LC-MS/MS analysis tentatively identified 43 bioactive constituents in the ethyl acetate fraction of Madeng’ai (MEA), including flavonoids, phenolic acids, and fatty acids. • MEA significantly alleviated LPS-induced acute lung injury in mice by reducing pulmonary edema, inflammatory cell infiltration, and pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β). • Integrated multi-omics and network pharmacology revealed that MEA exerts protective effects via multi-target regulation of the TLR4/NF-κB and PI3K/AKT signaling pathways, as well as metabolic reprogramming of fatty acid and amino acid metabolism. • This study provides a systematic multi-omics-based strategy for dissecting the mechanisms of traditional ethnic medicine, supporting the potential of MEA as a promising adjuvant therapeutic agent for acute lung injury (ALI).