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张婷婷,刘博,邹雪,满益娟,张宝昕.基于网络药理学和实验验证探讨加味小柴胡汤治疗咳嗽变异性哮喘的分子机制[J].湖南中医药大学学报英文版,2024,44(3):419-426.[Click to copy
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| 基于网络药理学和实验验证探讨加味小柴胡汤治疗咳嗽变异性哮喘的分子机制 |
| 张婷婷,刘博,邹雪,满益娟,张宝昕 |
| (河北省沧州中西医结合医院儿科, 河北 沧州 061001) |
| 摘要: |
| 目的 通过网络药理学、分子对接和实验验证对加味小柴胡汤治疗咳嗽变异性哮喘的主要活性成分及潜在作用机制进行探讨。方法 应用网络药理学预测加味小柴胡汤治疗咳嗽变异性哮喘可能的作用机制，并通过分子对接预测活性成分的结合位点。构建哮喘大鼠模型，将60只大鼠随机分为正常组、模型组、地塞米松片组[0.5 mg/（kg·d）]、加味小柴胡汤组[5 g/（kg·d）]，每组15只。正常组、模型组给予生理盐水2 mL灌胃，每日灌胃2次。给药4周后取大鼠血清及肺组织，ELISA法检测血清白细胞介素-6（interleukin-6， IL-6）、白细胞介素-13（interleukin-13， IL-13）、免疫球蛋白E（immunoglobulin E， IgE）、干扰素-γ（interferon-γ， INF-γ）水平，Western blot法检测肺组织丝裂原活化蛋白激酶（mitogen-activated protein kinase， MAPK）、GATA结合蛋白-3（GATA-binding protein-3， GATA-3）表达水平。结果 网络药理学共筛选出加味小柴胡汤有效成分1 483种，作用靶点274个，咳嗽变异性哮喘相关靶点7 509个，其交集靶点204个。GO和KEGG富集分析主要涉及信号转导、炎症反应、细胞凋亡等一系列的生物学反应过程，主要参与表皮生长因子受体（epidermal growth factor receptor， EGFR）、丝裂原活化蛋白激酶1（mitogen-activated protein kinase 1， MAPK1）、丝裂原活化蛋白激酶3（mitogen-activated protein kinase 3， MAPK3）、RELA癌基因（RELA proto-oncogene， RELA）、细胞肿瘤抗原p53（cellular tumor antigen P53， TP53）、细胞性骨髓细胞瘤病病毒癌（myelocytomatosis virus carcinoma， MYC）和蛋白激酶Cα（protein kinase Cα， PRKCA）等靶点的调控。分子对接结果表明，筛选得到的主要活性成分与靶点有较强的结合力。与正常组比较，模型组大鼠肺组织中IL-6、IL-13、IgE、MAPK、GATA-3升高（P<0.05），INF-γ降低（P<0.05）。与模型组比较，地塞米松片组及加味小柴胡汤组IL-6、IL-13、IgE、MAPK、GATA-3降低（P<0.05），INF-γ升高（P<0.05）。与地塞米松片组比较，加味小柴胡汤组大鼠IL-6、IL-13、IgE降低（P<0.05），INF-γ升高（P<0.05）。结论 加味小柴胡汤对咳嗽变异性哮喘具有治疗作用，其作用机制可能与EGFR、MAPK1、MAPK3、RELA、TP53、MYC和PRKCA靶点有关。 |
| 关键词: 加味小柴胡汤 咳嗽变异性哮喘 表皮生长因子受体 丝裂原活化蛋白激酶 RELA癌基因 地塞米松 分子对接 |
| DOI：10.3969/j.issn.1674-070X.2024.03.010 |
| Received:July 16, 2023 |
| 基金项目:河北省中医药管理局科研计划项目（2021317）。 |
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| Molecular mechanism of Jiawei Xiaochaihu Decoction in treating cough-variant asthma based on network pharmacology and experimental validation |
| ZHANG Tingting,LIU Bo,ZOU Xue,MAN Yijuan,ZHANG Baoxin |
| (Pediatric Department, Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou, Hebei 061001, China) |
| Abstract: |
| Objective To explore the main active ingredients and potential mechanism of action of Jiawei Xiaochaihu Decoction (JWXCHD) in treating cough-variant asthma through network pharmacology, molecular docking, and experimental validation. Methods The network pharmacology was applied to predicting the possible mechanism of action of JWXCHD in treating cough-variant asthma and molecular docking was used to predict the binding sites of active ingredients. A rat model of asthma was established, and 60 rats were randomly divided into normal group, model group, dexamethasone tablets group [0.5 mg/(kg·d)], and JWXCHD group [5 g/(kg·d)], with 15 rats in each group. The normal group and model group were given 2 mL of saline by gavage, twice a day. The serum and lung tissue of rats were collected after four weeks of administration. The levels of interleukin-6 (IL-6), interleukin-13 (IL-13), immunoglobulin E (IgE), and interferon-γ (INF-γ) were checked by ELISA, and the expression levels of mitogen-activated protein kinase (MAPK) and GATA-binding protein-3 (GATA-3) in the lung tissue were examined by Western blot. Results Network pharmacology screened out a total of 1,483 active ingredients of JWXCHD, 274 action targets, 7,509 targets related to cough-variant asthma, and 204 intersection targets. GO and KEGG enrichment analyses yielded a series of biological reaction processes such as signal transduction, inflammatory response, and cell apoptosis, mainly involving the regulation of targets such as epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), RELA proto-oncogene (RELA), cellular tumor antigen P53 (TP53), myelocytomatosis virus carcinoma (MYC), and protein kinase Cα (PRKCA). The results of molecular docking showed that the main active ingredients screened out had strong binding force with the targets. Compared with the normal group, IL-6, IL-13, IgE, MAPK, and GATA-3 increased (P<0.05) and INF-γ decreased (P<0.05) in the lung tissue of the model group. Compared with the model group, IL-6, IL-13, IgE, MAPK, and GATA-3 decreased (P<0.05) and INF-γ increased (P<0.05) in the lung tissue of the dexamethasone tablets group and the JWXCHD group. Compared with the dexamethasone tablets group, IL-6, IL-13, and IgE decreased and INF-γ increased in the JWXCHD group (P<0.05). Conclusion JWXCHD has therapeutic effects on cough-variant asthma, and its mechanism of action may be related to targets of EGFR, MAPK1, MAPK3, RELA, TP53, MYC, and PRKCA. |
| Key words: Jiawei Xiaochaihu Decoction cough-variant asthma epidermal growth factor receptor mitogen-activated protein kinase RELA proto-oncogene dexamethasone molecular docking |
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