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基于分子对接验证的贝母瓜蒌散治疗支气管扩张作用机制的网络药理学分析

Network Pharmacology Analysis of the Therapeutic Mechanisms Underlying Beimu-Gualou Formula Activity against Bronchiectasis with Molecular Docking Validation.

作者信息

Shen Xin, Li Hong, Zou Wen-Jun, Wu Jian-Ming, Wang Long, Wang Wei, Chen Hui, Zhou Ling-Li, Hu Yuan-Hui, Qin Xu-Hua, Yang Jing

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China.

School of Pharmacy, Southwest Medical University, Luzhou 646000, China.

出版信息

Evid Based Complement Alternat Med. 2021 Jan 5;2021:3656272. doi: 10.1155/2021/3656272. eCollection 2021.

Abstract

BACKGROUND

The classical Chinese herbal prescription Beimu-Gualou formula (BMGLF) has been diffusely applied to the treatment of respiratory diseases, including bronchiectasis. Although concerning bronchiectasis the effects and mechanisms of action of the BMGLF constituents have been partially elucidated, it remains to be determined how the formula in its entirety exerts therapeutic effects.

METHODS

In this study, the multitarget mechanisms of BMGLF against bronchiectasis were predicted with network pharmacology analysis. Using prepared data, a drug-target interaction network was established and subsequently the core therapeutic targets of BMGLF were identified. Furthermore, the biological function and pathway enrichment of potential targets were analyzed to evaluate the therapeutic effects and pivotal signaling pathways of BMGLF. Finally, virtual molecular docking was performed to assess the affinities of compounds for the candidate targets.

RESULTS

The therapeutic action of BMGLF against bronchiectasis involves 18 core target proteins, including the aforementioned candidates (i.e., ALB, ICAM1, IL10, and MAPK1), which are assumed to be related to biological processes such as drug response, cellular response to lipopolysaccharide, immune response, and positive regulation of NF-B activity in bronchiectasis. Among the top 20 signaling pathways identified, mechanisms of action appear to be primarily related to Chagas disease, allograft rejection, hepatitis B, and inflammatory bowel disease.

CONCLUSION

In summary, using a network pharmacology approach, we initially predicted the complex regulatory profile of BMGLF against bronchiectasis in which multilink suppression of immune/inflammatory responses plays an essential role. These results may provide a basis for novel pharmacotherapeutic approaches for bronchiectasis.

摘要

背景

中药经典方剂贝母瓜蒌散(BMGLF)已广泛应用于包括支气管扩张症在内的呼吸系统疾病的治疗。尽管BMGLF各成分对支气管扩张症的作用及作用机制已部分阐明,但该方剂整体如何发挥治疗作用仍有待确定。

方法

在本研究中,采用网络药理学分析预测BMGLF抗支气管扩张症的多靶点机制。利用已准备好的数据建立药物-靶点相互作用网络,随后确定BMGLF的核心治疗靶点。此外,分析潜在靶点的生物学功能和通路富集情况,以评估BMGLF的治疗作用和关键信号通路。最后,进行虚拟分子对接以评估化合物与候选靶点的亲和力。

结果

BMGLF对支气管扩张症的治疗作用涉及18种核心靶蛋白,包括上述候选蛋白(即ALB、ICAM1、IL10和MAPK1),这些蛋白被认为与支气管扩张症中的药物反应、细胞对脂多糖的反应、免疫反应以及NF-κB活性的正调控等生物学过程有关。在鉴定出的前20条信号通路中,作用机制似乎主要与恰加斯病(南美锥虫病)、同种异体移植排斥、乙型肝炎和炎症性肠病有关。

结论

总之,我们采用网络药理学方法初步预测了BMGLF对支气管扩张症的复杂调控概况,其中对免疫/炎症反应的多环节抑制起关键作用。这些结果可能为支气管扩张症的新型药物治疗方法提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/628c/7803403/e0ef84404612/ECAM2021-3656272.001.jpg

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