基于网络药理学与分子对接技术探讨宁脂胶囊治疗高脂血症的作用机制

doi:10.16352/j.issn.1001-6325.2024.03.0346

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (3): 346-351.doi: 10.16352/j.issn.1001-6325.2024.03.0346

基于网络药理学与分子对接技术探讨宁脂胶囊治疗高脂血症的作用机制

谢昊¹, 李耀洋², 赵彬¹, 杨丹², 吴群励^2*

中国医学科学院北京协和医学院北京协和医院 1. 药剂科;2. 中医科,北京 100730

收稿日期:2023-10-31 修回日期:2023-12-27 出版日期:2024-03-05 发布日期:2024-02-22
通讯作者: ^*:chinlie@163.com
基金资助:
国家中医药管理局青年岐黄学者培养项目(国中医药人教函【2022】256号);北京协和医院中央高水平医院临床科研专项青年培优计划项目(2022-PUMCH-A-211);北京协和医院中央高水平医院临床科研专项专科提升计划项目(2022-PUMCH-B-121)

Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology

XIE Hao¹, LI Yaoyang², ZHAO Bin¹, YANG Dan², WU Qunli^2*

1. Department of Pharmacy; 2. Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China

Received:2023-10-31 Revised:2023-12-27 Online:2024-03-05 Published:2024-02-22
Contact: ^*:chinlie@163.com

摘要/Abstract

摘要： 目的筛选降脂中药宁脂胶囊的潜在药理靶点,探讨其作用机制。方法通过BATMAN-TCM数据库获取宁脂胶囊组成药物的成分及预测靶点;通过DisGeNET与GeneCards数据库获取高脂血症相关靶点。使用Venny2.1.0工具对药物靶点和疾病靶点进行映射,获得共同靶点,作为潜在药理靶点。接着对共同靶点进行蛋白质互作分析(STRING)、基因本体论及通路富集分析(DAVID)。最后使用SwissDock进行分子对接验证。结果发现宁脂胶囊预测靶点1 432个,高脂血症相关靶点87个,筛选两者共同靶点32个,涉及宁脂胶囊64种潜在药理成分。其中郁金、姜黄、蒲黄的潜在药理靶点最多;决明子、姜黄、郁金的潜在药理成分最多。载脂蛋白E(APOE)、一氧化氮合酶3(NOS3)和过氧化物酶体增殖物激活受体α(PPARA)的高脂血症相关性评分最高,蛋白质互作较多,为潜在核心靶点。DNA转录相关生物学过程被显著富集,胆固醇代谢、cGMP-PKG、PPAR信号通路分别涉及APOE、NOS3、PPARA。分子对接显示结合活性较好。结论宁脂胶囊的潜在药理成分较多,降脂的关键药物包括郁金、姜黄、蒲黄和决明子。APOE,NOS3和PPARA可能是降脂的关键靶点,其作用机制可能与胆固醇代谢、cGMP-PKG和PPAR信号通路相关。

关键词: 宁脂胶囊, 高脂血症, 网络药理学, 靶点, 通路

Abstract: Objective To screen the potential pharmacological targets of Ningzhi capsule, a lipid-lowering traditional Chinese medicine, and explore its mechanism of effect. Methods The components and predicted targets of Ningzhi capsule′s constituent drugs were obtained from BATMAN-TCM database. Hyperlipidemia-related targets were obtained from DisGeNET and GeneCards databases. The Venny2.1.0 tool was used to map drug targets and disease targets to obtain common targets as potential pharmacological targets. Protein-protein interaction analysis (STRING), gene ontology and pathway enrichment analysis (DAVID) were performed for the common targets. Finally, Swiss dock was used for molecular docking verification. Results A total of 1 432 predicted targets of Ningzhi capsule and 87 targets related to hyperlipidemia were found and 32 common targets were screened which covered 64 potential pharmacological ingredients of Ningzhi capsule. Potential pharmacological targets were most abundant for turmeric root-tuber, turmeric and cattail pollen, and potential pharmacological ingredients were most abundant for sickle senna seed, turmeric and turmeric root-tuber. Apolipoprotein E (APOE), nitric oxide synthase 3 (NOS3) and peroxisome proliferator activated receptor alpha (PPARA) had the highest hyperlipidemia correlation scores and more protein interactions, which were potential core targets. The biological processes related to DNA transcription were significantly enriched. Cholesterol metabolism, cGMP-PKG and PPAR signaling pathways were involved with APOE, NOS3 and PPARA, respectively. Molecular docking showed good binding activity. Conclusions There are many potential pharmacological ingredients of Ningzhi capsule and the key components for lowering lipids include turmeric root-tuber, turmeric, cattail pollen and sickle senna seed. APOE, NOS3 and PPARA are believed to be the key targets for lowering lipids with potential mechanism related to cholesterol metabolism, cGMP-PKG and PPAR signaling pathways.

Key words: Ningzhi capsule, hyperlipidemia, network pharmacology, target, pathway

中图分类号:

R285

谢昊, 李耀洋, 赵彬, 杨丹, 吴群励. 基于网络药理学与分子对接技术探讨宁脂胶囊治疗高脂血症的作用机制[J]. 基础医学与临床, 2024, 44(3): 346-351.

XIE Hao, LI Yaoyang, ZHAO Bin, YANG Dan, WU Qunli. Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology[J]. Basic & Clinical Medicine, 2024, 44(3): 346-351.

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基于网络药理学与分子对接技术探讨宁脂胶囊治疗高脂血症的作用机制

Mechanism of treating hyperlipidemia with Ningzhi capsule based on network pharmacology and molecular docking technology

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