Department of Pulmonary and Critical Care Medicine, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, Zhejiang Province, China.
Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Nantong, 298 Xinhua Road, Chongchuan District, Nantong, 226002, Jiangsu, China.
Biomed Eng Online. 2021 Dec 14;20(1):125. doi: 10.1186/s12938-021-00965-6.
Wogonin (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).
Lipopolysaccharide (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.
LPS 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.
Wogonin 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.
白杨素（5,7-二羟基-8-甲氧基黄酮）是从黄芩根中提取的一种天然二羟基黄酮类化合物。本文旨在研究白杨素缓解急性肺损伤（ALI）中炎症和细胞凋亡的作用机制。
采用脂多糖（LPS）建立体外 ALI 模型。用白杨素处理后，分别通过 CCK-8 法、TUNEL 法和吖啶橙/溴化乙锭双重染色法测定 LPS 诱导的 A549 细胞活力和凋亡，通过 RT-qPCR、ELISA 法、Western blot 分析和商业试剂盒测定炎症细胞因子和氧化应激标志物的含量。Western blot 也用于评估相关蛋白的表达。随后，研究了白杨素对 SIRT1 介导的高迁移率族蛋白 1（HMGB1）去乙酰化的影响。用 SIRT1 抑制剂 EX527 评价 LPS 刺激下白杨素对 SIRT1 介导的 HMGB1 去乙酰化的调节作用。
LPS 诱导 A549 细胞炎症、氧化应激和凋亡，而白杨素则消除了这些作用。还发现，白杨素促进了 HMGB1 的去乙酰化，同时 SIRT1 表达上调。然而，SIRT1 抑制剂 EX527 部分逆转了白杨素对 LPS 诱导的 A549 细胞炎症和凋亡的保护作用。
白杨素通过 SIRT1 介导的 HMGB1 去乙酰化缓解 LPS 诱导的 A549 细胞炎症和凋亡，这可能代表了白杨素对 ALI 发挥保护作用的新机制，并为将白杨素应用于 ALI 治疗提供了思路。
