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甘草干姜汤通过靶向唾液酸结合免疫球蛋白样凝集素-1抑制慢性阻塞性肺疾病中的炎症并减轻线粒体功能障碍。

Licorice and dried ginger decoction inhibits inflammation and alleviates mitochondrial dysfunction in chronic obstructive pulmonary disease by targeting siglec-1.

作者信息

Li Sensen, Cao Juan, Yang Zhongjie, Jin Shaoju, Yang Lei, Chen Hao

机构信息

Department of Scientific Research Section, the First People's Hospital of Zhumadian, Affiliated Hospital of Huanghuai University, Zhumadian, Henan 463000, China; Zhumadian Key Laboratory of Chronic Disease Research, School of Medicine, Huanghuai University, Zhumadian, Henan 463000, China.

Department of Scientific Research Section, the First People's Hospital of Zhumadian, Affiliated Hospital of Huanghuai University, Zhumadian, Henan 463000, China; Zhumadian Key Laboratory of Chronic Disease Research, School of Medicine, Huanghuai University, Zhumadian, Henan 463000, China.

出版信息

Int Immunopharmacol. 2025 Jan 27;146:113789. doi: 10.1016/j.intimp.2024.113789. Epub 2024 Dec 21.

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease. Licorice and dried ginger decoction (LGD) is traditional Chinese medicine prescription with multiple effects. Glycyrrhetinic acid (GA) is the main bioactive components of LGD, which has been proven to have a relieving effect on various inflammatory diseases. Siglec-1 is a cell surface sialoadhesin and has been confirmed to be overexpressed in COPD and facilitate inflammatory reaction. This study is aimed to probe the interaction between LGD, GA, and siglec-1.

METHODS

Cigarette smoke (CS) combined with lipopolysaccharide (LPS) treatment was utilized to construct a COPD rat model. Cigarette smoke extract (CSE) was utilized to induce alveolar macrophage NR8383 to construct a COPD cell model. HE staining was applied for measuring histopathological changes of COPD rats. Enzyme-linked immunosorbent assay (ELISA), reverse transcription real-time polymerase chain reaction (RT-qPCR), and western blot were applied for testing the concentrations and expressions of proinflammatory factors. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS) analysis was utilized to determine the combination between siglec-1 and GA. JC-1 assay was utilized to evaluate mitochondrial function. Reactive oxygen species (ROS) production was tested by dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining.

RESULTS

LGD treatment notably alleviated lung injury and inflammatory response in COPD rats. In CSE-induced cells, LGD treatment suppressed the contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8. Sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression induced by CS was decreased after LGD treatment. Furthermore, we proved that GA could target siglec-1 to regulate the inflammatory response in COPD rats and cells. Additionally, GA could reduce ROS production and alleviate mitochondrial dysfunction to suppress COPD progression.

CONCLUSION

LGD inhibits inflammation and alleviates mitochondrial dysfunction in COPD by targeting siglec-1.

摘要

背景

慢性阻塞性肺疾病(COPD)是一种慢性呼吸道疾病。甘草干姜汤(LGD)是一种具有多种功效的中药方剂。甘草次酸(GA)是LGD的主要生物活性成分,已被证明对各种炎症性疾病具有缓解作用。唾液酸结合免疫球蛋白样凝集素1(Siglec-1)是一种细胞表面唾液酸黏附素,已证实在COPD中过度表达并促进炎症反应。本研究旨在探讨LGD、GA和Siglec-1之间的相互作用。

方法

采用香烟烟雾(CS)联合脂多糖(LPS)处理构建COPD大鼠模型。利用香烟烟雾提取物(CSE)诱导肺泡巨噬细胞NR8383构建COPD细胞模型。采用苏木精-伊红(HE)染色检测COPD大鼠的组织病理学变化。采用酶联免疫吸附测定(ELISA)、逆转录实时聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法检测促炎因子的浓度和表达。利用高效液相色谱-串联质谱(HPLC-MS)分析确定Siglec-1与GA之间的结合。采用JC-1检测法评估线粒体功能。用二氯二氢荧光素二乙酸酯(DCFH-DA)染色检测活性氧(ROS)的产生。

结果

LGD治疗显著减轻了COPD大鼠的肺损伤和炎症反应。在CSE诱导的细胞中,LGD治疗抑制了肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6和IL-8的含量。LGD治疗后,CS诱导的唾液酸结合免疫球蛋白样凝集素1(Siglec-1)表达降低。此外,我们证明GA可以靶向Siglec-1来调节COPD大鼠和细胞中的炎症反应。此外,GA可以减少ROS的产生并减轻线粒体功能障碍,从而抑制COPD的进展。

结论

LGD通过靶向Siglec-1抑制COPD中的炎症并减轻线粒体功能障碍。

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