Background: Astragaloside II (AST II) is one of the principal bioactive components of Astragalus mongholicus Bunge, exhibiting multiple pharmacological properties. However, the therapeutic efficacy of AST II in Chronic Obstructive Pulmonary Disease (COPD) remains to be fully elucidated. The study explored the effects and mechanisms of AST II in a COPD model induced by exposure to cigarette smoke (CS) and lipopolysaccharide (LPS) in mice.
Methods: An animal model of COPD was established by intratracheal instillation of LPS and cigarette smoking in mice. Serum samples were collected to determine inflammatory cell infiltration and cytokine levels. Lung tissues were collected for histological, immunofluorescence and Western blot analysis. The RAW264.7 macrophage cell line was employed to investigate the molecular mechanism of AST II in vitro.
Results: Lung dysfunction, histopathological damage, inflammatory infiltration, and pro-inflammatory factors secretion in COPD mice induced by CS and LPS were mitigated by AST II. AST II exerted an anti-inflammatory effect by enhancing the activation of the mammalian target of rapamycin complex 1 (mTORC1)/glycogen synthase kinase-3β (GSK-3β) signaling pathway, which promoted the binding of CREB-binding protein (CBP) to CREB, thereby antagonizing the binding to nuclear factor-κB (NF-κB) and inhibiting its transcriptional activity. However, AST II did not demonstrate a protective effect against LPS-induced inflammatory damage to RAW264.7 cells when mTORC1 was inhibited by rapamycin.
Conclusion: AST II exhibits potential therapeutic benefits as an alternative medication for COPD and other respiratory inflammatory conditions since it may reduce lung injury and inflammatory response in mice exposed to CS and LPS.
Keywords: Astragaloside II; COPD; Inflammation; mTORC1/GSK-3β signaling pathway.
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