Apigenin Attenuates Transverse Aortic Constriction-Induced Myocardial Hypertrophy: The Key Role of miR-185-5p/SREBP2-Mediated Autophagy.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-08-27 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S464004

Na Yan, Xianggui Wang, Zufang Xu, Linling Zhong, Jiangyong Yang

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引用次数: 0

Abstract

Introduction: Apigenin is a natural flavonoid compound with promising potential for the attenuation of myocardial hypertrophy (MH). The compound can also modulate the expression of miR-185-5p that both promote MH and suppress autophagy. The current attempts to explain the anti-MH effect of apigenin by focusing on changes in miR-185-5p-mediated autophagy.

Methods: Hypertrophic symptoms were induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using Ang II and then handled with apigenin. Changes in myocardial function and structure and cell viability and surface area were measured. The role of miR-185-5p in the anti-MH function of apigenin was explored by detecting changes in autophagic processes and miR-185-5p/SREBP2 axis.

Results: TAC surgery induced weight increase, structure destruction, and collagen deposition in hearts of model rats. Ang II suppresses cardiomyocyte viability and increased cell surface area. All these impairments were attenuated by apigenin and were associated with the restored level of autophagy. At the molecular level, the expression of miR-185-5p was up-regulated by TAC, while the expression of SREBP2 was down-regulated, which was reserved by apigenin both in vivo and in vitro. The induction of miR-185-5p in cardiomyocytes could counteracted the protective effects of apigenin.

Discussion: Collectively, the findings outlined in the current study highlighted that apigenin showed anti-MH effects. The effects were related to the inhibition of miR-185-5p and activation of SREBP, which contributed to the increased autophagy.

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芹菜素能减轻横向主动脉收缩诱导的心肌肥厚：miR-185-5p/SREBP2 介导的自噬的关键作用

简介芹菜素是一种天然类黄酮化合物，具有减轻心肌肥厚（MH）的潜力。该化合物还能调节 miR-185-5p 的表达，而 miR-185-5p 既能促进心肌肥厚，又能抑制自噬。方法：用横向主动脉收缩法（TAC）诱导大鼠出现肥厚症状，用 Ang II 诱导心肌细胞出现肥厚症状，然后用芹菜素处理。测量了心肌功能和结构的变化以及细胞活力和表面积。通过检测自噬过程和 miR-185-5p/SREBP2 轴的变化，探讨了 miR-185-5p 在芹菜素抗 MH 功能中的作用：结果：TAC手术导致模型大鼠心脏重量增加、结构破坏和胶原沉积。血管紧张素 II 可抑制心肌细胞活力并增加细胞表面积。芹菜素减轻了所有这些损伤，并与自噬水平的恢复有关。在分子水平上，TAC 上调了 miR-185-5p 的表达，同时下调了 SREBP2 的表达。心肌细胞中miR-185-5p的诱导可抵消芹菜素的保护作用：总之，本研究概述的发现突出表明芹菜素具有抗心肌缺血的作用。这些作用与抑制 miR-185-5p 和激活 SREBP 有关，而后者有助于增加自噬。

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.