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

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.

AMPK: The key to ischemia‐reperfusion injury

“…Alleviating the lung tissue damage caused by an excessive inflammatory reaction in lung IRI is an important way to resist lung IRI. Mangiferin via the SIRT1/AMPK signaling pathway, OMEGA‐3 polyunsaturated fatty acid ( ω −3 PUFA) via the AMPK/SIRT1 signaling pathway, and dexmedetomidine via HMGB1/NLRP3 inflammasome/AMPK pathway all play a role in regulating the inflammatory response in lung IRI, such as reducing the levels of IL‐1β and TNF‐α inflammatory factors and reducing the infiltration of white blood cells (X. Chen & Huang, 2021; Y. Chen et al, 2020; H. Jing et al, 2014). Specifically, ω −3 PUFA and DEX can prevent intestinal IRI and renal IRI‐derived pulmonary IRI, respectively.…”