Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China.
Department of Cardiovascular Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China.
Mol Divers. 2024 Aug;28(4):2603-2616. doi: 10.1007/s11030-023-10700-z. Epub 2023 Jul 24.
Pulmonary hypertension, a common complication of chronic obstructive pulmonary disease, is a major global health concern. Green tea is a popular beverage that is consumed all over the world. Green tea's active ingredients are epicatechin derivatives, also known as "polyphenols," which have anti-carcinogenic, anti-inflammatory, and antioxidant properties. This study aimed to explore the possible mechanism of green tea polyphenols in the treatment of pulmonary hypertension using network pharmacology, molecular docking, and experimental verification. A total of 316 potential green tea polyphenols-related targets were obtained from the PharmMapper, SwissTargetPrediction, and TargetNet databases. A total of 410 pulmonary hypertension-related targets were predicted by the CTD, DisGeNET, pharmkb, and GeneCards databases. Green tea polyphenols-related targets were hit by the 49 targets associated with pulmonary hypertension. AKT1 and HIF1-α were identified through the FDA drugs-target network and PPI network combined with GO functional annotation and KEGG pathway enrichment. Molecular docking results showed that green tea polyphenols had strong binding abilities to AKT1 and HIF1-α. In vitro experiments showed that green tea polyphenols inhibited the proliferation and migration of hypoxia stimulated pulmonary artery smooth muscle cells by decreasing AKT1 phosphorylation and downregulating HIF1α expression. Collectively, green tea polyphenols are promising phytochemicals against pulmonary hypertension.
肺动脉高压是慢性阻塞性肺疾病的常见并发症，是一个全球性的重大健康问题。绿茶是一种在世界各地都很受欢迎的饮料。绿茶的活性成分是儿茶素衍生物，也称为“多酚”，具有抗癌、抗炎和抗氧化特性。本研究旨在通过网络药理学、分子对接和实验验证来探讨绿茶多酚治疗肺动脉高压的可能机制。从 PharmMapper、SwissTargetPrediction 和 TargetNet 数据库中获得了 316 种潜在的绿茶多酚相关靶点。通过 CTD、DisGeNET、pharmkb 和 GeneCards 数据库预测了 410 个与肺动脉高压相关的靶点。绿茶多酚相关靶点与与肺动脉高压相关的 49 个靶点发生碰撞。通过 FDA 药物-靶点网络和 PPI 网络结合 GO 功能注释和 KEGG 通路富集，鉴定出 AKT1 和 HIF1-α。分子对接结果表明，绿茶多酚对 AKT1 和 HIF1-α 具有很强的结合能力。体外实验表明，绿茶多酚通过降低 AKT1 磷酸化和下调 HIF1α 表达来抑制缺氧刺激的肺动脉平滑肌细胞的增殖和迁移。总之，绿茶多酚是一种有前途的治疗肺动脉高压的植物化学物质。
