Wang Jingxi, Wang Hongyang, Kang Xin, Wang Xiaotian, Li Xi, Guo Jie, Jing Xuan, Chu Xi, Han Xue
The First Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation, Shijiazhuang, China.
Sci Rep. 2025 Apr 1;15(1):11024. doi: 10.1038/s41598-025-95810-4.
Hesperetin (HE), a natural flavonoid exhibiting anti-inflammatory and antioxidant properties, holds significant potential in treating chronic obstructive pulmonary disease (COPD). Nonetheless, the precise mechanisms underlying its effects are yet to be fully elucidated. In this study, we aim to explore the role and potential mechanism of HE in treating COPD using network pharmacology, molecular docking and experimental validation. We screened for HE and COPD-related targets from public databases, and then imported potential targets into a STRING database to establish a protein-protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis were performed to obtain key signaling pathways. We then predicted the binding interactions between HE and core targets using molecular docking. The animal model of COPD was established through lipopolysaccharide and cigarette smoke induction in mice to observe lung function, inflammatory factors, pathology, and the expression of related proteins. Network pharmacology findings unveiled that HE and COPD shared 105 common targets. MAPKs and NF-κB signaling pathways were selected for further validation. In animal experiment, HE enhanced lung function and histopathological morphology, while reducing inflammation levels. The results of Western blot tests indicated that HE treatment considerably inhibited the expression of MAPKs and NF-κB. HE effectively reduced lung inflammation and improved lung function in mice. This mechanism may be achieved by inhibition of MAPKs and NF-κB signaling pathways.
橙皮素（HE）是一种具有抗炎和抗氧化特性的天然黄酮类化合物，在治疗慢性阻塞性肺疾病（COPD）方面具有巨大潜力。然而，其作用的精确机制尚未完全阐明。在本研究中，我们旨在利用网络药理学、分子对接和实验验证来探索HE在治疗COPD中的作用和潜在机制。我们从公共数据库中筛选出HE和COPD相关靶点，然后将潜在靶点导入STRING数据库以建立蛋白质-蛋白质相互作用网络。进行基因本体（GO）和京都基因与基因组百科全书富集分析以获得关键信号通路。然后我们使用分子对接预测HE与核心靶点之间的结合相互作用。通过脂多糖和香烟烟雾诱导建立小鼠COPD动物模型，以观察肺功能、炎症因子、病理学及相关蛋白的表达。网络药理学研究结果表明，HE与COPD共有105个共同靶点。选择丝裂原活化蛋白激酶（MAPKs）和核因子κB（NF-κB）信号通路进行进一步验证。在动物实验中，HE增强了肺功能和组织病理学形态，同时降低了炎症水平。蛋白质免疫印迹试验结果表明，HE治疗显著抑制了MAPKs和NF-κB的表达。HE有效减轻了小鼠肺部炎症并改善了肺功能。这一机制可能是通过抑制MAPKs和NF-κB信号通路实现的。
