Angong niuhuang wan attenuates LPS-induced acute lung injury by inhibiting PIK3CG/p65/MMP9 signaling in mice based on proteomics.

Angong niuhuang wan attenuates LPS-induced acute lung injury by inhibiting PIK3CG/p65/MMP9 signaling in mice based on proteomics.
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DOI:
10.1016/j.heliyon.2023.e20149
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发表时间:
2023-09
期刊:
影响因子:
4
通讯作者:
Li, Xianyu
Li, Xianyu
中科院分区:
综合性期刊4区
文献类型:
--
作者:
Li, Sen;Hou, Jinli;Wang, Qing;Liu, Mei;Xu, Xingyue;Yang, Hongjun;Li, Xianyu

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急性肺损伤(acute lung injury,ALI)是一种严重的肺部并发症,通常由肺炎、细菌或病毒引起的呼吸道感染以及其他因素引起。其特点是发病急、死亡率高。安宫牛黄丸是我国著名的中医急症药,被誉为“凉开三宝”,被誉为“三宝”之首。已有研究证实,AGNHW具有抗炎、改善脑循环、减轻脑水肿、保护血管内皮等作用。然而,AGNHW治疗ALI的活性成分和药理机制尚不清楚。在本研究中,我们证实了AGNHW可以抑制细胞因子风暴活性,减轻LPS诱导的ALI小鼠炎症反应。然后,我们使用蛋白质组学技术分析差异蛋白,并确定了741个差异蛋白。结合网络药理学分析,深入探讨了青蒿琥酯治疗急性肺损伤的关键活性成分及其作用机制。通过构建疾病和药物之间的相互作用网络,我们确定了21个关键活性成分(如槲皮素,山奈酚和藏红花酸)和25个潜在的核心靶点(如PIK 3CG,p65和MMP 9)。这些候选靶点在抗炎和免疫调节中发挥重要作用。通过对核心靶点的富集分析,我们发现了几条与ALI相关的信号通路,如NF-κB信号通路、TNF信号通路和Toll样受体信号通路。提示AGNHW通过多组分、多靶点、多途径对ALI发挥治疗作用。
Acute lung injury (ALI) is a serious pulmonary complication that often arises from pneumonia, respiratory tract infections caused by bacteria or viruses, and other factors. It is characterized by acute onset and high mortality. Angong Niuhuang Wan (AGNHW) is a renowned emergency medicine in traditional Chinese medicine, known as the "cool open (febrile disease) three treasures" and regarded as the first of the "three treasures". Previously studies have confirmed that AGNHW has anti-inflammatory effects, improves cerebral circulation, reduces brain edema, and protects vascular endothelium. However, the active components and pharmacological mechanisms of AGNHW in treating ALI remain unclear. In this study, we confirmed that AGNHW can inhibit cytokine storm activity and reduce inflammation induced by LPS in ALI mice. We then analyzed differential proteins using proteomic technology and identified 741 differential proteins. By combining network pharmacological analysis, we deeply discussed the key active components and mechanism of AGNHW in treating ALI. By constructing the interaction network between disease and drug, we identified 21 key active components (such as Quercetin, Kaempferol, and Crocetin) and 25 potential core targets (such as PIK3CG, p65, and MMP9). These candidate targets play an important role in anti-inflammation and immune regulation. Through enrichment analysis of core targets, we found several pathways related to ALI, such as the NF-κB signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. This indicates that AGNHW plays a therapeutic role in ALI through multi-components, multi-targets, and multi-pathways.
橙皮苷/壳聚糖纳米颗粒的鼻递送可抑制急性肺损伤小鼠模型中的细胞因子风暴综合征
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