网络药理学与实验验证相结合,阐明桂枝甘草煎剂治疗苯肾上腺素诱发的心肌肥大的作用机制。

IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Pharmaceutical Biology Pub Date : 2024-12-01 Epub Date: 2024-05-21 DOI:10.1080/13880209.2024.2354335
Kaijing Yang, Xiaoli Shan, Yang Songru, Mengwei Fu, Pei Zhao, Wei Guo, Ming Xu, Huihua Chen, Rong Lu, Chen Zhang
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引用次数: 0

摘要

背景中药桂枝甘草汤(GGD)的作用机制尚不清楚:本研究探讨了桂枝甘草汤抗心肌肥厚的机制:材料和方法:通过网络药理学分析,确定了GGD的潜在靶点。在体内实验中,将 C57BL/6J 小鼠分为 Con、苯肾上腺素(PE,10 mg/kg/d)、2-氯腺苷(CADO,腺苷的稳定类似物,2 mg/kg/d)、GGD(5.4 g/kg/d)和 GGD(5.4 g/kg/d)+ CGS15943(一种非选择性腺苷受体拮抗剂,4 mg/kg/d)。在体外实验中,原代新生大鼠心肌细胞(NRCM)被分为 Con、PE(100 µM)、CADO(5 µM)、GGD(10-5 g/mL)和 GGD(10-5 g/mL)+ CGS15943(5 µM)。通过超声波、H&E 和 Masson 染色、肥大基因表达和细胞表面积来验证 GGD 的功效。通过实时聚合酶链反应(PCR)、Western 印迹和免疫荧光分析检测腺苷受体(ADORs)的表达:结果:网络药理学发现 ADORs 是 GGD 的核心靶点之一。体外实验表明,GGD 可减轻 PE 引起的表面积增加(EC50 为 5.484 × 10-6 g/mL)。体内数据显示,GGD 可减轻 PE 引起的心室壁增厚。体外和体内数据表明,GGD 可减轻 PE 诱导的肥大基因表达(如 ANP、BNP 和 MYH7/MYH6)、A1AR 过度表达和 A2aAR 表达降低。此外,CADO 的作用与 GGD 相似,而 CGS15943 则消除了 GGD 的大部分作用:我们的研究结果表明了 GGD 抑制心肌肥厚的机制,并强调调节 ADORs 是治疗高血压的一种潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.

Context: The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.

Objective: This study explores the mechanisms of GGD against cardiac hypertrophy.

Materials and methods: Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10-5 g/mL) and GGD (10-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.

Results: Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10-6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.

Discussion and conclusions: Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

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来源期刊
Pharmaceutical Biology
Pharmaceutical Biology 医学-药学
CiteScore
6.70
自引率
2.60%
发文量
191
审稿时长
1 months
期刊介绍: Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine. Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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