State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China; Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030032, China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China.
J Ethnopharmacol. 2023 Oct 5;314:116544. doi: 10.1016/j.jep.2023.116544. Epub 2023 Apr 22.
Pulmonary artery hypertension (PAH) is a progressive and fatal lung disease of multifactorial etiology, which arouses an enhanced interest in PAH disease therapy. Modified Fangji Huangqi decoction (MFJHQ), a traditional Chinese medicine (TCM) formula, has a crucial role in the treatment of PAH. However, the pharmacological roles and mechanisms of MFJHQ on PAH remain unknown.
To investigate the effects and potential mechanism of MFJHQ on pulmonary vascular remodeling in PAH.
Ultra-performance liquid chromatography (UPLC) was employed to quantitate the principal components in MFJHQ. Rats were treated with MFJHQ by gavage for final 2 weeks in monocrotaline (MCT)-induced PAH rats. RNA-sequencing and network pharmacology analysis were performed to explore the potential mechanism. The primary rat pulmonary artery smooth muscle cells (PASMCs) were utilized to evaluate the regulatory effect of MFJHQ in vitro.
Seven active components from MFJHQ were quantitated by UPLC. In rats with MCT-induced PAH, MFJHQ treatment significantly improved hemodynamic parameters, right ventricular hypertrophy index, lung function, and attenuated pulmonary vascular remodeling. Mechanistically, we further confirmed that MFJHQ inhibits MCT-induced phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) pathway predicated by network pharmacology and RNA-sequencing analysis to reduce the proliferation of pulmonary arteries and promote pulmonary artery apoptosis in lung tissues. Additionally, MFJHQ hindered the proliferation and migration, and accelerated apoptosis in PDGF-BB-induced PASMCs in vitro, which can be enhanced by the presence of the PI3K inhibitor LY294002.
Our results indicated that MFJHQ inhibited MCT-induced pulmonary vascular remodeling by decreasing proliferation and migration of PASMCs and promoting PASMC apoptosis through PI3K/Akt pathway, which provides a novel treatment option for PAH with multi-targeting mechanisms inspired by TCM theory.
肺动脉高压（PAH）是一种多因素病因引起的进行性和致命性肺部疾病，这引起了人们对 PAH 疾病治疗的极大兴趣。改良防己黄芪汤（MFJHQ）是一种中药（TCM）配方，在 PAH 的治疗中起着至关重要的作用。然而，MFJHQ 对 PAH 的药理作用和机制尚不清楚。
探讨 MFJHQ 对 PAH 肺血管重构的影响及其潜在机制。
采用超高效液相色谱（UPLC）定量测定 MFJHQ 中的主要成分。用 MFJHQ 灌胃治疗 2 周，最后 2 周在野百合碱（MCT）诱导的 PAH 大鼠中。进行 RNA 测序和网络药理学分析以探索潜在机制。体外利用原代大鼠肺动脉平滑肌细胞（PASMCs）评估 MFJHQ 的调节作用。
通过 UPLC 定量测定 MFJHQ 中的 7 种活性成分。在 MCT 诱导的 PAH 大鼠中，MFJHQ 治疗可显著改善血流动力学参数、右心室肥厚指数、肺功能，并减轻肺血管重构。在机制上，我们进一步证实 MFJHQ 通过网络药理学和 RNA 测序分析预测的抑制 MCT 诱导的磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）通路，减少肺动脉增殖并促进肺组织中的肺动脉细胞凋亡。此外，MFJHQ 可抑制 PDGF-BB 诱导的 PASMCs 的增殖和迁移，并促进其凋亡，而 PI3K 抑制剂 LY294002 可增强其作用。
我们的研究结果表明，MFJHQ 通过降低 PASMC 的增殖和迁移并通过 PI3K/Akt 通路促进 PASMC 凋亡来抑制 MCT 诱导的肺血管重构，这为基于 TCM 理论的多靶点机制治疗 PAH 提供了新的治疗选择。
