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

Hualiang Jin; Limin Wang; Bei Li; Cui Cai; Jian Ye; Junbo Xia; Shenglin Ma

doi:10.1155/2017/4037086

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

Evid Based Complement Alternat Med. 2017:2017:4037086. doi: 10.1155/2017/4037086. Epub 2017 Oct 25.

Authors

Hualiang Jin^{1

2}, Limin Wang^{1

2}, Bei Li³, Cui Cai⁴, Jian Ye^{1

2}, Junbo Xia^{1

2}, Shenglin Ma^{1

5}

Affiliations

¹ Department of Respiratory Diseases, Hangzhou First People's Hospital, The Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.
² Department of Respiratory Diseases, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, China.
³ Department of Geriatric Medicine, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, China.
⁴ Department of Geriatric Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310002, China.
⁵ Department of Oncology, Hangzhou First People's Hospital, The Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.

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.