Panax notoginseng Saponins Improve Angiogenesis in Coronary Heart Disease Based on the microRNA 200a Methylation Pathway.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-12-18 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S488036

Jie Wang, Yan Dong, Zhaoling Li, Yun Zhang, Lanchun Liu, Guang Yang, Yongmei Liu, Jun Li, Lian Duan

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引用次数: 0

Abstract

Background: Improving angiogenesis in the ischemic myocardium is a therapeutic strategy for preventing, reducing, and repairing myocardial injury of coronary artery disease (CAD). Panax notoginseng saponins (PNS) have been widely used in the clinical treatment of cardiovascular diseases, demonstrating excellent efficacy, and can potentially improve angiogenesis in the ischemic myocardium. However, the effects of PNS on angiogenesis and its underlying mechanism of action remain unclear.

Purpose: In this study, we aimed to evaluate the role of PNS in improving angiogenesis after myocardial infarction (MI) and explain the mechanism of PNS in improving angiogenesis in CAD from an epigenetic perspective.

Study design: The MI rat model was established by ligating the left anterior descending coronary artery permanently. The in vitro model comprised hypoxic human coronary artery endothelial cells (HCEACs). The mice and cells were then treated with PNS.

Methods: Blood tests, histomorphology, polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and MassARRAY targeted methylation detection analyses were conducted in vivo and in vitro to investigate the potential mechanisms of PNS.

Results: Oral PNS significantly improved myocardial injury and activated angiogenesis in MI rats. DNA methylation analysis in vitro revealed that PNS decreased the hypermethylation of microRNA 200a (miR200a). PNS improved angiogenesis in hypoxic human coronary artery endothelial cells (HCEACs) by regulating the vascular endothelial growth factor (VEGF) pathway.

Conclusion: Our research shows that PNS can improve angiogenesis in rats with MI and hypoxic HCEACs and affect the level of miR200a promoter methylation and miR200a and VEGF molecular pathways.

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三七皂苷通过microRNA 200a甲基化途径促进冠心病血管生成

背景：促进缺血心肌血管生成是预防、减轻和修复冠心病心肌损伤的一种治疗策略。三七皂苷（PNS）已广泛应用于心血管疾病的临床治疗，显示出优异的疗效，并可能促进缺血心肌的血管生成。然而，PNS对血管生成的影响及其作用机制尚不清楚。目的：本研究旨在评价PNS对心肌梗死（MI）后血管生成的促进作用，并从表观遗传学角度解释PNS促进冠心病（CAD）血管生成的机制。研究设计：采用冠状动脉左前降支永久结扎法建立心肌梗死大鼠模型。体外模型由缺氧人冠状动脉内皮细胞（HCEACs）组成。然后用PNS处理小鼠和细胞。方法：采用体内和体外血液检测、组织形态学、聚合酶链反应、酶联免疫吸附试验、Western blotting和MassARRAY靶向甲基化检测分析，探讨PNS的潜在机制。结果：口服PNS可显著改善心肌梗死大鼠心肌损伤，激活血管生成。体外DNA甲基化分析显示，PNS降低了microRNA 200a （miR200a）的高甲基化。PNS通过调节血管内皮生长因子（VEGF）通路促进缺氧人冠状动脉内皮细胞（HCEACs）的血管生成。结论：我们的研究表明，PNS可以促进心肌梗死和缺氧HCEACs大鼠的血管生成，并影响miR200a启动子甲基化水平以及miR200a和VEGF分子通路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.