School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
Yantai Center for Food and Drug Control, Yantai, 264003, China.
J Pharm Pharmacol. 2024 Oct 3;76(10):1340-1351. doi: 10.1093/jpp/rgae071.
To unveil the mechanism of the Bufei Huoxue formula (BHF) for chronic obstructive pulmonary disease (COPD) through integrated network pharmacology (NP) and experimental verification.
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.
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.
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.
通过整合网络药理学（NP）和实验验证，揭示补肺活血方（BHF）治疗慢性阻塞性肺疾病（COPD）的作用机制。
首先采用 LC-MS 对 BHF 的体外和体内样本进行化学分析，然后制备一个配体库，用于 NP 以揭示 BHF 治疗 COPD 的作用机制。最后，使用与 NP 结果相关的动物模型进行验证。
从 BHF 中获得了一个含有 170 种化合物的配体库，同时筛选出 357 个与 COPD 相关的靶点，构建了一个 PPI 网络。GO 和 KEGG 分析表明，补骨脂素、芍药苷和芒柄花素去甲基化是 BHF 治疗 COPD 的主要化合物，主要通过调节 PI3K/Akt 通路。实验证明 BHF 可以在一定剂量范围内减轻肺损伤，减轻 TNF-α和 IL-6 在肺和 BALF 中的释放。Western blot 进一步表明 BHF 对 p-PI3K 有下调作用。
BHF 为 COPD 的治疗提供了一种有效的替代方法，其作用机制可能与通过补骨脂素、芍药苷和芒柄花素去甲基化调节 PI3K/AKT 通路来减轻炎症损伤有关。
