Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Chen,Xianfeng; Huang,Juanjuan

doi:10.3892/etm.2021.10654

Mangiferin inhibits hypoxia/reoxygenation‑induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway

Authors:
- Xianfeng Chen
- Juanjuan Huang
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Affiliations: Department of Traditional Chinese Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Published online on: August 26, 2021 https://doi.org/10.3892/etm.2021.10654
Article Number: 1220
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung ischemia‑reperfusion injury (LIRI) is one of the complications that can occur after lung transplantation and may lead to morbidity and mortality. Mangiferin (MAF) is a naturally occurring glucosyl xanthone that has been documented to possess anti‑inflammatory, immunomodulatory and potent antioxidant effects. The purpose of the present study was to investigate the effect of MAF on LIRI using a hypoxia‑reoxygenation (H/R) cell model. In the present study, the viability of lung alveolar epithelial cells (A549) and H/R‑A549 were detected by MTT assay. ELISA was used to evaluate the expression levels of IL‑6 and IL‑1β. TUNEL assay and western blotting were used to evaluate the apoptosis. In addition, H/R‑A549 cells were treated with sirtinol, which is known inhibitor of sirtuin 1 (SIRT1) activity, to determine the effects of MAF on proteins associated with the SIRT1/5'AMP‑activate protein kinase (AMPK) signaling pathway using western blotting. The results showed that 20 µM MAF exerted a protective effect on A549 cells against H/R mediating no clear cytotoxic effects. In terms of inflammation, MAF reduced IL‑6, IL‑1β, cyclooxygenase‑2 and inducible nitric oxide synthase expression, which was accompanied by activation of the SIRT1/AMPK signaling pathway. In addition, compared with those in the group treated with sirtinol, expression of SIRT1, Bcl‑2 and AMPK activity were elevated in MAF‑treated H/R‑A549 cells, whereas the expression of Bax, cleaved caspase‑3 and cleaved caspase‑9 was suppressed. TUNEL analysis of H/R‑A549 cells treated with MAF in combination with sirtinol revealed that treatment with sirtinol blocked the SIRT1/AMPK signaling pathway and increased the apoptosis rate compared with the MAF group. Taken together, results of the present study revealed that MAF could inhibit lung H/R cell injury through the SIRT1/AMPK signaling pathway.

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