New insight into the molecular mechanism of TCM Bufei Huoxue formula for chronic obstructive pulmonary disease based on network pharmacology and experimental verification.

IF 2.8 4区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-08-21 DOI:10.1093/jpp/rgae071
Yuanying Zhu, Shengyuan Hao, Yan Wu, Yuxian Lin, Xuecun Liu, Ting Luo, Yubing Zhou, Xin Yang, Hui Xu
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Abstract

Objectives: To unveil the mechanism of the Bufei Huoxue formula (BHF) for chronic obstructive pulmonary disease (COPD) through integrated network pharmacology (NP) and experimental verification.

Methods: LC-MS was first applied to the analysis of both in vitro and in vivo samples from BHF for chemical profiling. Then a ligand library was prepared for NP to reveal the mechanism of BHF against COPD. Finally, verification was performed using an animal model related to the results from the NP.

Key findings: A ligand library containing 170 compounds from BHF was obtained, while 357 targets related to COPD were filtered to construct a PPI network. GO and KEGG analysis demonstrated that bavachin, paeoniflorin, and demethylation of formononetin were the major compounds for BHF against COPD, which mainly by regulating the PI3K/Akt pathway. The experiments proved that BHF could alleviate lung injury and attenuate the release of TNF-α and IL-6 in the lung and BALF in a dose-dependent manner. Western blot further demonstrated the down-regulated effect of BHF on p-PI3K.

Conclusion: BHF provides a potent alternative for the treatment of COPD, and the mechanism is probably associated with regulating the PI3K/AKT pathway to alleviate inflammatory injury by bavachin, paeoniflorin, and demethylation of formononetin.

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基于网络药理学和实验验证的慢性阻塞性肺疾病中药不老藿香正气液分子机制新认识
目的通过整合网络药理学(NP)和实验验证,揭示不老复方治疗慢性阻塞性肺病(COPD)的机理:方法:首先应用 LC-MS 分析 BHF 的体外和体内样本,进行化学谱分析。方法:首先应用 LC-MS 对 BHF 的体外和体内样本进行化学分析,然后为 NP 准备配体库,以揭示 BHF 抗慢性阻塞性肺病的机制。最后,利用与 NP 结果相关的动物模型进行了验证:获得了一个包含 170 种 BHF 化合物的配体库,并筛选出 357 个与慢性阻塞性肺病相关的靶点,从而构建了一个 PPI 网络。GO和KEGG分析表明,巴伐醌、芍药苷和去甲基甲萘素是BHF对抗慢性阻塞性肺病的主要化合物,它们主要通过调节PI3K/Akt通路。实验证明,BHF能减轻肺损伤,并以剂量依赖的方式减少肺和BALF中TNF-α和IL-6的释放。Western blot进一步证明了BHF对p-PI3K的下调作用:结论:BHF为慢性阻塞性肺病的治疗提供了一种有效的替代疗法,其机制可能与巴伐醌、芍药苷和去甲基甲萘素调节PI3K/AKT通路以减轻炎症损伤有关。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
91
审稿时长
3 months
期刊介绍: JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.
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