Monochasma savatieri Franch. protects against acute lung injury via 7nAChR-TLR4/NF-B p65 signaling pathway based on integrated pharmacology analysis

Ethnopharmacological relevance: Acute lung injury (ALI) is a life-threatening condition with high morbidity and mortality, underscoring the urgent need for novel treatments. Monochasma savatieri Franch. (LRC) is commonly used clinically to treat wind-heat cold, bronchitis, acute pneumonia and acute gastroenteritis. However, its role in the treatment of ALI and its mechanism of action are still unclear. Aim of the study: This study aimed to demonstrate the pharmacological effects and underlying mechanisms of LRC extract, and provide important therapeutic strategies and theoretical basis for ALI. Materials and methods: In this study, a research paradigm of integrated pharmacology combining histopathological analysis, network pharmacology, metabolomics, and biochemical assays was used to elucidate the mechanisms underlaying the effects of LRC extract on LPS-induced ALI in BALB/c mice. Results: The research findings demonstrated that LRC extract significantly alleviated pathological damage in lung tissues and inhibited apoptosis in alveolar epithelial cells, and the main active components were luteolin, isoacteoside, and aucubin. Lung tissue metabolomic and immunohistochemical methods confirmed that LRC extract could restore metabolic disorders in ALI mice by correcting energy metabolism imbalance, activating cholinergic anti-inflammatory pathway (CAP), and inhibiting TLR4/NF-kappa B signaling pathway. Conclusions: This study showed that LRC extract inhibited the occurrence and development of ALI inflammation by promoting the synthesis of antioxidant metabolites, balancing energy metabolism, activating CAP and suppressing the alpha 7nAChR-TLR4/NF-kappa B p65 signaling pathway. In addition, our study provided an innovative research model for exploring the effective ingredients and mechanisms of traditional Chinese medicine. To the best of our knowledge, this is the first report describing the protective effects of LRC extract in LPS-induced ALI mice.