网络药理学研究揭示连花清瘟-辛夷散联合治疗新冠后嗅觉损伤的潜在作用机制

doi:10.5246/jcps.2024.07.047

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (7): 631-646.DOI: 10.5246/jcps.2024.07.047

网络药理学研究揭示连花清瘟-辛夷散联合治疗新冠后嗅觉损伤的潜在作用机制

魏晓玉¹^,^#, 于路航²^,^#, 李梦茹³^,^#, 徐强⁴^,^*()

^1. 天津中医药大学, 天津 301617
^2. 中国人民解放军医学院, 中国人民解放军总医院, 北京 100853
^3. 天津中医药大学第一附属医院, 天津 300381
^4. 天津中医药大学第二附属医院, 天津 300250

收稿日期:2023-12-21 修回日期:2024-01-23 接受日期:2024-03-12 出版日期:2024-07-30 发布日期:2024-07-30
通讯作者: 徐强

A network pharmacological study to investigate the combination of LHQW-XYS in the treatment of COVID-19 olfactory impairment-associated

Xiaoyu Wei¹^,^#, Luhang Yu²^,^#, Mengru Li³^,^#, Qiang Xu⁴^,^*()

¹ Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
² Chinese PLA Medical School, Chinese People’s Liberation Army (PLA) General Hospital, Beijing 100853, China
³ First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
⁴ Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China

Received:2023-12-21 Revised:2024-01-23 Accepted:2024-03-12 Online:2024-07-30 Published:2024-07-30
Contact: Qiang Xu
About author:
^# Xiaoyu Wei, Luhang Yu and Mengru Li contributed equally to this work.
Supported by:
National Natural Science Foundation of China General Project (Grant No. 82374195).

摘要/Abstract

摘要：

本文旨在利用网络药理学方法探索连花清瘟-辛夷散对新冠嗅觉损伤主要成分的作用靶点, 并试图揭示其在新冠致嗅觉损伤相关治疗中的作用机制。我们利用TCMSP平台进行口服利用度和类药性筛选获取潜在有效成分; Swiss TargetPrediction平台预测有效成分的作用靶标, 构建药物-成分-作用靶标网络, 再通过GeneCards、OMIM、TTD平台获取新冠嗅觉损伤基因靶点, 将药物靶标和疾病基因相交集获得共同靶点。利用STRING及Cytoscape 3.8.2软件构建靶标-疾病基因PPI网络, 筛选关键靶点和核心基因团簇, 借助Metascape平台对关键靶点进行GO和KEGG富集分析, 并就筛选出来的核心有效成分及其作用靶标映射到通路中, 构建核心有效成分-靶标-通路网络, 最后进行分子对接。结果显示连花清瘟-辛夷散活性成分有4669个潜在靶点, 5609个疾病靶点和17个药物-疾病交叉靶点。GO和KEGG富集分析显示, 连花清瘟-辛夷散治疗新冠嗅觉损伤相关的机制可能是由于相关信号通路的调控作用, 如5-羟色胺能突触和脂肪细胞的脂解调节。分子对接结果表明, 6种活性成分(槲皮素、木犀草素、山奈酚、7-甲氧基-2-甲基异黄酮、汉黄芩素、美迪紫檀素)和2个关键基因(PTGS2、PPARG)具有良好的结合特性。综上我们可以得到结论: 连花清瘟-辛夷散可能通过作用于脂肪细胞中的5-羟色胺能突触和调节脂解通路, 从而实现治疗新冠嗅觉损伤的相关作用。

关键词: 连花清瘟-辛夷散, 新冠相关嗅觉损伤, 网络药理学, 分子对接

Abstract:

To explore the target of action of LHQW-XYS on the main components of COVID-19 olfactory impairment by using network pharmacological methods and try to reveal its mechanism of action in the treatment related to COVID-19 induced olfactory impairment, we used the TCMSP platform to obtain potential active ingredients through oral utilization and drug-like properties screening; the Swiss TargetPrediction platform to predict the targets of the active ingredients and construct a drug-ingredient-target network, and then obtained the gene targets of COVID-19 olfactory injury through GeneCards, OMIM, and TTD platforms to intersect the drug targets and disease genes to obtain common targets. The drug targets and disease genes were intersected to obtain common targets. STRING and Cytoscape 3.8.2 software were used to construct the target-disease gene PPI network, screen the key targets and core gene clusters, and analyze the key targets by GO and KEGG enrichment analyses with the help of the Metascape platform, and then map the screened core active ingredients and their targets into the pathway to construct the core active ingredients-targets-pathway network. The core active ingredient-target-pathway network was constructed, and finally, molecular docking was carried out. The results showed that there were 4669 potential targets, 5609 disease targets, and 17 drug-disease cross-targets for the active ingredients of LHQW-XYS. The GO and KEGG enrichment analyses indicated that the mechanism of LHQW-XYS in the treatment of olfactory impairment in COVID-19 may be due to the regulation of related signaling pathways, such as Serotonergic synapse and Regulation of lipolysis in adipocytes. Molecular docking showed that six active components (quercetin, luteolin, kaempferol, 7-methoxy-2-methylisoflavone, wogonin, medicarpin) and two key genes (PTGS2, PPARG) had good binding properties. In the end, we conclude that LHQW-XYS may act on Serotonergic synapse and Regulation of lipolysis in adipocyte pathways to achieve anti-COVID-19 olfactory impairment-associated effects.

Key words: LHQWXYS, COVID-19 olfactory impairment-associate, Network pharmacology, Molecular docking

Supporting:

魏晓玉, 于路航, 李梦茹, 徐强. 网络药理学研究揭示连花清瘟-辛夷散联合治疗新冠后嗅觉损伤的潜在作用机制[J]. 中国药学(英文版), 2024, 33(7): 631-646.

Xiaoyu Wei, Luhang Yu, Mengru Li, Qiang Xu. A network pharmacological study to investigate the combination of LHQW-XYS in the treatment of COVID-19 olfactory impairment-associated[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(7): 631-646.

图/表 7

Table 1. Information about the major active compounds in LHQW-XYS.

Figure 1. Venn maps of disease targets in different disease databases.

Figure 2. Venn diagram of possible LHQW-XYS targets treated with COVID-19 olfactory impairment.

Figure 3. Construction of a target modulation network for COVID-19 olfactory impairment treatment with LHQW-XYS.

Figure 4. (a) PPI network construction and core module of COVID-19 olfactory impairment and LHQW-XYS; (b) the most significant modules analyzed by the MCODE plugin.

Figure 5. (a) Intersection target GO enrichment analysis: biological process (BP), cell composition (CC), molecular function (MF); (b) KEGG enrichment analysis.

Figure 6. (a) Schematic diagram of PPARG-6FZG docking; (b) Schematic diagram of PTGS2-5IKR docking; (c) Core active ingredients and core protein binding energy (kcal/mol).

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网络药理学研究揭示连花清瘟-辛夷散联合治疗新冠后嗅觉损伤的潜在作用机制

A network pharmacological study to investigate the combination of LHQW-XYS in the treatment of COVID-19 olfactory impairment-associated

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