Danshensu methyl ester attenuated LPS-induced acute lung injury by inhibiting TLR4/NF-κB pathway

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xuejia Han , Wensi Ding , Guiwu Qu , Youjie Li , Pingyu Wang , Jiahui Yu , Mingyue Liu , Xiulan Chen , Shuyang Xie , Jiankai Feng , Sen Xu
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Abstract

Acute Lung Injury (ALI) manifests as an acute exacerbation of pulmonary inflammation with high mortality. The potential application of Danshensu methyl ester (DME, synthesized in our lab) in ameliorating ALI has not been elucidated. Our results demonstrated that DME led to a remarkable reduction in lung injury. DME promoted a marked increase in antioxidant enzymes, like superoxide dismutase (SOD), and glutathione (GSH), accompanied by a substantial decrease in reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA). Moreover, DME decreased the production of IL-1β, TNF-α and IL-6, in vitro and in vivo. TLR4 and MyD88 expression is reduced in the DME-treated cells or tissues, which further leading to a decrease of p-p65 and p-IκBα. Meanwhile, DME effectively facilitated an elevation in cytoplasmic p65 expression. In summary, DME could ameliorate ALI by its antioxidant functionality and anti-inflammation effects through TLR4/NF-κB, which implied that DME may be a viable medicine for lung injury.

Abstract Image

丹参素甲酯通过抑制 TLR4/NF-κB 通路减轻 LPS 诱导的急性肺损伤
急性肺损伤(ALI)表现为肺部炎症的急性加重,死亡率很高。丹参素甲酯(DME,由我们实验室合成)在改善急性肺损伤方面的潜在应用尚未阐明。我们的研究结果表明,丹参素甲酯能显著减轻肺损伤。DME促进了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)等抗氧化酶的明显增加,同时大幅减少了活性氧(ROS)、髓过氧化物酶(MPO)和丙二醛(MDA)。此外,DME 还能减少体外和体内 IL-1β、TNF-α 和 IL-6 的产生。TLR4和MyD88在经DME处理的细胞或组织中的表达减少,从而进一步导致p-p65和p-IκBα的减少。同时,DME能有效促进细胞质p65表达的增加。综上所述,二甲双胍可通过其抗氧化功能和TLR4/NF-κB的抗炎作用改善ALI,这意味着二甲双胍可能是一种治疗肺损伤的可行药物。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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