1. Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation.
- Author
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Gao ZD, Yan HD, Wu NH, Yao Q, Wan BB, Liu XF, Zhang ZW, Chen QJ, and Huang CP
- Subjects
- Animals, Flavanones, Male, Mice, Mice, Inbred C57BL, NF-kappa B metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Network Pharmacology, Phosphatidylinositol 3-Kinases, Acute Lung Injury chemically induced, Acute Lung Injury drug therapy, Lipopolysaccharides
- Abstract
Background: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response., Objectives: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms., Methods: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury., Findings: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis., Conclusion: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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