Huang Ping, Huang Tao, Li Deshun, Han Lintao, Zhou Zhenxiang, Huang Fang, Li Jingjing, Wu Jiajia, Ye Yan, Wang Qiong, Duan Bailu
College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China.
Wuhan Red Cross Hospital, Wuhan 430065, China.
Evid Based Complement Alternat Med. 2021 Jun 10;2021:5532009. doi: 10.1155/2021/5532009. eCollection 2021.
Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity, disability, and mortality, which seriously threatens human life and health. Xixin and Ganjiang are classic herb pairs of Zhongjing Zhang, which are often used to treat COPD in China. However, the substance basis and mechanism of action of Xixin-Ganjiang herb pair (XGHP) in the treatment of COPD remain unclear.
On the website of TCMSP and the DrugBank, effective compounds and targets of XGHP were found. COPD targets were obtained from GeneCards, DisGeNET, and GEO gene chips. Intersecting these databases resulted in a library of drug targets for COPD. Then, intersection targets were used for protein-protein interaction (PPI) and pathway enrichment analysis. Finally, the binding activity between compounds and core genes was evaluated by molecular docking to verify the expression level of PTGS2 and PPARG in rats.
Twelve effective compounds and 104 core genes were found in the intersection library, and kaempferol, sesamin, -sitosterol, PTGS2, and PPARG were particularly prominent in the network analysis. A total of 113 pathways were obtained and enrichment of the TNF signaling pathway, IL-17 signaling pathway, and C-type lectin receptor signaling pathway was particularly obvious. Molecular docking indicated that kaempferol, sesamin, and -sitosterol were closely related to PTGS2 and PPARG and were superior to aminophylline. Key compounds in XGHP could restrict the expression of PTGS2 in the lung tissues of COPD rats and promote the expression of PPARG.
Inhibition of the expression of inflammatory factor PTGS2 and promotion of the expression of PPARG may be an effective target of XGHP in the treatment of COPD.
慢性阻塞性肺疾病（COPD）具有高发病率、高致残率和高死亡率的特点，严重威胁人类生命健康。细辛和干姜是张仲景的经典药对，在中国常用于治疗COPD。然而，细辛 - 干姜药对（XGHP）治疗COPD的物质基础和作用机制尚不清楚。
在中药系统药理学数据库与分析平台（TCMSP）网站和药物银行（DrugBank）上查找XGHP的有效化合物和靶点。从基因卡片（GeneCards）、疾病基因数据库（DisGeNET）和基因表达综合数据库（GEO）基因芯片中获取COPD靶点。将这些数据库进行交叉分析，得到COPD的药物靶点库。然后，对交叉靶点进行蛋白质 - 蛋白质相互作用（PPI）和通路富集分析。最后，通过分子对接评估化合物与核心基因之间的结合活性，以验证大鼠中环氧合酶 - 2（PTGS2）和过氧化物酶体增殖物激活受体γ（PPARG）的表达水平。
在交叉库中发现了12种有效化合物和104个核心基因，山奈酚、芝麻素、β - 谷甾醇、PTGS2和PPARG在网络分析中尤为突出。共获得113条通路，肿瘤坏死因子（TNF）信号通路、白细胞介素 - 17（IL - 17）信号通路和C型凝集素受体信号通路的富集尤为明显。分子对接表明，山奈酚、芝麻素和β - 谷甾醇与PTGS2和PPARG密切相关，且优于氨茶碱。XGHP中的关键化合物可抑制COPD大鼠肺组织中PTGS2的表达，并促进PPARG的表达。
抑制炎症因子PTGS2的表达并促进PPARG的表达可能是XGHP治疗COPD的有效靶点。
