Astragaloside IV Ameliorates Airway Inflammation in an Established Murine Model of Asthma by Inhibiting the mTORC1 Signaling Pathway

Abstract

Astragaloside IV (AS‐IV), a main active constituent of Astragalus membranaceus , has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS‐IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS‐IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL‐4, IL‐5, IL‐13, IL‐17, and INF‐ γ ), and CD4 + CD25 + Foxp3 + Treg cells in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling were examined. AS‐IV markedly suppressed airway hyperresponsiveness and reduced IL‐4, IL‐5, and IL‐17 levels and increased INF‐ γ levels in the BALF. Histological studies showed that AS‐IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS‐IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4 + CD25 + Foxp3 + Treg cells in BALF were not significantly changed by AS‐IV. Together, these results suggest that the antiasthmatic effects of AS‐IV were at least partially from inhibiting the mTORC1 signaling pathway.