Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis.

IF 3.9 3区医学 Q1 MEDICAL LABORATORY TECHNOLOGY

Pharmaceutical Biology Pub Date : 2022-12-01 DOI:10.1080/13880209.2022.2123934

Fuqiong Zhou, Zhengguang Zhang, Meiyuan Wang, Weina Zhu, Jie Ruan, Hongyan Long, Yajie Zhang, Ning Gu

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引用次数: 1

Abstract

Context: Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear.

Objective: To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism.

Materials and methods: Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results.

Results: In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC₅₀ = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins.

Conclusions: GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

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冠心V通过调节铁稳态减轻心肌缺血再灌注损伤。

背景:冠心V (GX)是一种安全有效的治疗冠心病的中药方剂。然而，其对心肌缺血再灌注损伤(MIRI)的保护作用尚不清楚。目的:探讨GX对MIRI的心脏保护作用，并探讨其可能机制。材料与方法:将sd - dawley雄性大鼠分为Sham、MIRI和MIRI + GX组。GX (6 g/kg)在缺血再灌注(IR)手术前7天灌胃给药。观察梗死面积、组织病理学、血清酶活性、心肌线粒体超微结构。H9c2细胞用GX (0.5 mg/mL)预处理，然后缺氧/再氧化(HR)。测定细胞活力和LDH水平。运用网络药理学方法预测其潜在机制。利用TCMSP数据库、DrugBank数据库等对GX的相关靶点进行预测。最后通过药理实验对预测结果进行验证。结果:GX在体内使心肌梗死面积从56.33%降低至17.18%，降低AST (239.32 vs. 369.18 U/L)、CK-MB (1324.61 vs. 2066.47 U/L)、LDH (1245.26 vs. 1969.62 U/L)水平，减轻线粒体损伤。GX在体外显著提高H9c2细胞活力(IC50 = 3.913 mg/mL)，抑制LDH释放(207.35 vs. 314.33)。此外，GX还能通过调节铁代谢相关蛋白来维持铁稳态，降低氧化应激水平。结论:GX可以通过调节铁稳态来减轻MIRI，表明GX可能是治疗MIRI的潜在候选药物。

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

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.