Abstract

BackgroundWogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI).Materials and methodsLipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation.ResultsLPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells.ConclusionWogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.

Highlights

  • Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi

  • Wogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by sirtuin 1 (SIRT1)-mediated highmobility group box 1 protein (HMGB1) deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on acute lung injury (ALI) and provide ideas for the application of wogonin to ALI treatment

  • Effects of wogonin on the viability and apoptosis of LPS‐induced A549 cells To observe the effect of wogonin on ALI, we first speculated if the viability of normal A549 cells could be damaged by wogonin

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Summary

Introduction

Wogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root of Scutellaria baicalensis Georgi. Acute lung injury (ALI) is clinically documented as the result of the pathological states including sepsis, pneumonia, trauma, and acute pancreatitis [1]. It is often seen in patients who are admitted into the intensive care units and shows a high mortality rate [2]. Those who survive from ALI are usually confronted with inferior quality of life [3]. Current evidence suggested that the inflammatory response and ALI induced by LPS could be attenuated as a result of wogonin treatment by peroxisome proliferator-activated receptor gamma (PPARγ)-mediated

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