Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by excessive proliferation and vasoconstriction of small pulmonary artery vascular smooth muscle cells (PASMCs). Coptidis rhizoma (CR) because of the complexity of the components, the underlying pharmacological role and mechanism of it on PAH remains unknown. In this article, the network pharmacological analysis was used to screen the main active constituents of CR and the molecular targets that these constituents act on. Then, we evaluated the importance of berberine and quercetin (biologically active components of CR) on the proliferation and migration of PASMCs and vascular remodeling in experimental models of PAH. Our results showed that berberine and quercetin effectively inhibited the proliferation and migration of hypoxia-induced PASMCs in a manner likely to be mediated by the suppression of MAPK1, NADPH oxidase 4 (NOX4), and cytochrome P450 1B1 (CYP1B1) expression. Furthermore, berberine and quercetin treatment attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension in rat models. In conclusion, this research demonstrates CR might be a promising treatment option for PAH, and the network pharmacology approach can be an effective tool to reveal the potential mechanisms of Chinese herbal medicine.

中文翻译：

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黄连中的生物活性化合物通过抑制肺动脉平滑肌细胞的增殖和迁移来缓解肺动脉高压。


肺动脉高压（PAH）是一种破坏性疾病，其特征是小肺动脉血管平滑肌细胞（PASMC）过度增殖和血管收缩。黄连(CR)由于成分复杂，其治疗PAH的药理作用和机制仍不清楚。本文采用网络药理学分析方法筛选CR的主要活性成分以及这些成分作用的分子靶点。然后，我们评估了小檗碱和槲皮素（CR 的生物活性成分）对 PASMC 的增殖和迁移以及 PAH 实验模型中血管重塑的重要性。我们的结果表明，小檗碱和槲皮素有效抑制缺氧诱导的 PASMC 的增殖和迁移，其机制可能是通过抑制 MAPK1、NADPH 氧化酶 4 (NOX4) 和细胞色素 P450 1B1 (CYP1B1) 的表达来介导。此外，在野百合碱诱导的肺动脉高压大鼠模型中，小檗碱和槲皮素治疗可减轻肺动脉高压，减少右心室肥厚，并改善肺动脉重塑。总之，这项研究表明 CR 可能是 PAH 的一种有前途的治疗选择，而网络药理学方法可以成为揭示中草药潜在机制的有效工具。