Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China.
Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
Biol Chem. 2023 Mar 6;405(2):119-128. doi: 10.1515/hsz-2022-0316. Print 2024 Feb 26.
() root as a traditional herb is widely applied to pharmacotherapy for vascular system disease. In this study, we elucidate the therapy mechanism of by using a model of hindlimb ischemia. Blood perfusion measurement showed that intravenous administration of the Water Extract of (WES) could facilitate damaged hindlimb blood flow recovery and blood vessel regeneration. mRNA screen assay in cultured human umbilical vein endothelial cells (HUVECs) show that WES induced increased , and mRNA levels. Endothelial NOS (eNOS) promotor reporter analysis revealed that WES and the major ingredients danshensu (DSS) could enhance eNOS promoter activity. Additionally, we found that WES and its ingredients, including DSS, protocatechuic aldehyde (PAI), and salvianolic acid A (SaA), promoted HUVECs growth by the endothelial cell viability assays. A mechanistic approach confirmed that WES augments HUVECs proliferation through the activation of extracellular signal-regulated kinase (ERK) signal pathway. This study reveals that WES promotes ischemic remodeling and angiogenesis through its multiple principal ingredients, which target and regulate multiple sites of the network of the blood vessel endothelial cell regenerating process.
丹参作为一种传统草药，被广泛应用于血管系统疾病的药物治疗。在这项研究中，我们通过后肢缺血模型阐明了丹参的治疗机制。血流灌注测量表明，丹参水提取物（WES）的静脉给药可促进受损后肢血流恢复和血管再生。在培养的人脐静脉内皮细胞（HUVECs）中进行的 mRNA 筛选分析显示，WES 诱导增加了 、 和 mRNA 水平。内皮型一氧化氮合酶（eNOS）启动子报告分析显示，WES 和主要成分丹参素（DSS）可以增强 eNOS 启动子活性。此外，我们发现 WES 及其成分，包括丹参素、原儿茶醛（PAI）和丹酚酸 A（SaA），通过内皮细胞活力测定促进 HUVECs 的生长。一种机制方法证实，WES 通过激活细胞外信号调节激酶（ERK）信号通路来增强 HUVECs 的增殖。这项研究揭示了 WES 通过其多种主要成分促进缺血性重塑和血管生成，这些成分针对并调节血管内皮细胞再生过程网络中的多个位点。
