陈皮预防慢性阻塞性肺疾病及其进展为肺癌的机制和候选化合物
The mechanism and candidate compounds of aged citrus peel () preventing chronic obstructive pulmonary disease and its progression to lung cancer.
作者信息
Zhou Lin, Gu Wenwen, Kui Fuguang, Gao Fan, Niu Yuji, Li Wenwen, Zhang Yaru, Guo Lijuan, Wang Junru, Guo Zhenzhen, Du Gangjun
机构信息
Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng, China.
School of Pharmacy and Chemical Engineering, Zhengzhou University of Industry Technology, Xinzheng, China.
出版信息
Food Nutr Res. 2021 May 17;65. doi: 10.29219/fnr.v65.7526. eCollection 2021.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is an important risk factor for developing lung cancer. Aged citrus peel () has been used as a dietary supplement for respiratory diseases in China.
OBJECTIVE
To explore the mechanism and candidate compounds of preventing COPD and its progression to lung cancer.
METHODS
The active components and potential targets of were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease-associated targets of COPD and lung cancer were collected in the Gene Cards and TTD database. The component-target network and PPI network were constructed using the Cytoscape 3.8.0 software. David database was used for GO and KEGG enrichment analysis. The main active components were verified by using the autodock Vina 1.1.2 software. Mouse lung cancer with COPD was induced by cigarette smoking (CS) combined with urethane injection to confirm preventing the effect of hesperetin (the candidate compound of ) on COPD progression to lung cancer and its underlying mechanisms.
RESULTS
The network analysis revealed that the key active components of (nobiletin, naringenin, hesperetin) regulate five core targets (AKT1, TP53, IL6, VEGFA, MMP9). In addition, 103 potential pathways of were identified. can prevent COPD and its progression to lung cancer by getting involved in the PI3K-Akt signaling pathway and MAPK signaling pathway. Molecular docking indicated that hesperetin had better binding activity for core targets. In mouse lung cancer with COPD, treatment with hesperetin dose-dependently improved not only lung tissue injury in COPD but also carcinoma lesions in lung cancer. Meanwhile, hesperetin could suppress the protein expression of AKT1, IL6, VEGFA, MMP9 and up-regulate the protein expression of TP53, and thus reduced the risk of COPD progression to lung cancer.
CONCLUSION
Hesperetin is a candidate compound of that helps in preventing COPD and its progression to lung cancer by regulating AKT1, IL6, VEGFA, MMP9 and TP53.
背景
慢性阻塞性肺疾病（COPD）是肺癌发生的重要危险因素。陈皮在中国已被用作呼吸系统疾病的膳食补充剂。
目的
探讨陈皮预防COPD及其进展为肺癌的机制和候选化合物。
方法
从中药系统药理学（TCMSP）数据库中检索陈皮的活性成分和潜在靶点。在基因卡片和TTD数据库中收集COPD和肺癌的疾病相关靶点。使用Cytoscape 3.8.0软件构建成分-靶点网络和蛋白质-蛋白质相互作用（PPI）网络。利用David数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。使用autodock Vina 1.1.2软件验证主要活性成分。通过香烟烟雾（CS）联合氨基甲酸乙酯注射诱导患有COPD的小鼠肺癌，以确认橙皮素（陈皮的候选化合物）对COPD进展为肺癌的预防作用及其潜在机制。
结果
网络分析显示，陈皮的关键活性成分（川陈皮素、柚皮素、橙皮素）调节五个核心靶点（AKT1、TP53、IL6、VEGFA、MMP9）。此外，确定了陈皮的103条潜在途径。陈皮可通过参与PI3K-Akt信号通路和丝裂原活化蛋白激酶（MAPK）信号通路来预防COPD及其进展为肺癌。分子对接表明，橙皮素对核心靶点具有更好的结合活性。在患有COPD的小鼠肺癌中，橙皮素治疗不仅剂量依赖性地改善了COPD中的肺组织损伤，还改善了肺癌中的癌性病变。同时，橙皮素可抑制AKT1、IL6、VEGFA、MMP9的蛋白表达，并上调TP53的蛋白表达，从而降低COPD进展为肺癌的风险。
结论
橙皮素是陈皮的候选化合物，通过调节AKT1、IL6、VEGFA、MMP9和TP53有助于预防COPD及其进展为肺癌。
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