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Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa , was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI. • Acute lung injury is a life-threatening disease without effective treatments now. • Forsythia suspense is used to treat pneumonia with its anti-inflammatory activity. • Forsythoside A is a natural product from Forsythia suspense. • Forsythoside A protects mice from lipopolysaccharide-induced acute lung injury. [ABSTRACT FROM AUTHOR]

• Component screening by intelligent MS data analysis and network pharmacology. • BE-DDA for non-targeted acquiring HRMS2 Data of TCM' s metabolites in vivo. • First report on comprehensive study on in vivo exposure of Xiaokewan in rats. Xiaokewan is a typical Traditional Chinese medicine (TCM) for diabetes and contains various natural chemicals, such as lignans, flavonoids, saponins, polysaccharides, and western medicine glibenclamide. In the current study, a highly efficient system for screening hypoglycemic efficacy constituents of Xiaokewan has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer assisted target fishing. With the combination of background exclusion data dependent acquisition (BE-DDA) and non-targeted precise-and-thorough background-subtraction (PATBS) techniques, a novel workflow has been established for the non-targeted recognition and identification of TCM constituents in vivo, and has been applied to the exposure study of Xiaokewan in rat. In this case, an interesting correlation among drug, target, and disease can be established, by combining the screening or characterization results with the strategy of network pharmacology and multiple computer assisted techniques. Consequently, five main constituents (puerarin, daidzein, formononetin, deoxyschizandrin and glibenclamide) exposed in vivo have been selected as effective hypoglycemic components. Meanwhile, the network pharmacology experimental results showed that these five constituents could act on various drug targets, such as PI3K, PTP1B, MAPK, AKT, TNF, and NF-κB. These five constituents might be involved in the regulation of β-cell function or exhibit inflammation inhibition ability to relieve the pathophysiological process of disease from multiple links. Furthermore, the pharmacological effects of these five constituents have been verified by diabetic zebrafish model. The zebrafish model results showed that the TCM monomer mixture without glibenclamide exhibited similar hypoglycemic activity with Xiaokewan. Although the monomer mixture with glibenclamide showed better activity than Xiaokewan only, the deoxyschizandrin (TCM constituent of Xiaokewan) exhibited best hypoglycemic performance. In summary, the above results indicated that the application of both intelligent recognition technology in mass spectrometry dataset and computerized network pharmacology might provide a pioneering approach for investigating the substance basis of TCM and searching lead compounds from natural sources. [ABSTRACT FROM AUTHOR]