Cardioprotective effects of S-equol, a soybean metabolite with estrogen activity, and role of the PI3K/Akt pathway in a male rat model of ischemic reperfusion

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids Pub Date : 2024-11-28 DOI:10.1016/j.steroids.2024.109542

Mariko Yamada , Yosuke Nakadate , Keisuke Omiya , Takeshi Oguchi , Masako Abe , Takashi Matsukawa

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引用次数: 0

Abstract

Purpose

S-equol, an isoflavone metabolite with high estrogenic activity, exhibits organ-protective effects via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. While estrogen has cardioprotective effects against ischemia–reperfusion injury, whether S-equol shares this capability remains uncertain. This study aimed to assess the cardioprotective effects of S-equol on stunned myocardium using an isolated rat heart model and investigate the involvement of PI3K/Akt signaling pathway.

Methods

Male rat hearts were perfused using the Langendorff system and divided into four groups: 1) modified Krebs–Henseleit (KH) buffer containing 1 μmol/L S-equol (EQ); 2) KH buffer (Cont); 3) KH buffer supplemented with 1 μmol/L S-equol and 100 nmol/L wortmannin (a specific PI3K inhibitor) (EQW); or 4) KH buffer containing wortmannin (ContW). After stabilization, each group was perfused for 20 min before undergoing 7.5 min of no-flow ischemia, followed by 20 min reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (left ventricle [LV] dP/dt max) after 20 min of reperfusion. Myocardial Akt and glycogen synthase kinase-3 beta (GSK-3β) were assayed using western blotting.

Results

LV dP/dt max was greater in the EQ group than that in the Cont group after 15 and 20 min of reperfusion; however, this effect was attenuated in the presence of PI3K inhibitors. S-equol treatment increased Akt and suppressed GSK-3β expression in the EQ group compared to that in the Cont group. However, these effects were not observed in the presence of wortmannin.

Conclusion

S-equol exerts a protective effect against myocardial ischemia–reperfusion injury, possibly by activating PI3K/Akt signaling.

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s -雌马酚（一种具有雌激素活性的大豆代谢物）在雄性大鼠缺血再灌注模型中的心脏保护作用及PI3K/Akt通路的作用

马雌醇是一种具有高雌激素活性的异黄酮代谢物，通过磷脂酰肌醇3-激酶/蛋白激酶B （PI3K/Akt）信号通路表现出器官保护作用。虽然雌激素对缺血再灌注损伤具有心脏保护作用，但雌马酚是否具有这种功能仍不确定。本研究旨在通过离体大鼠心脏模型评估s -马雌酚对休克心肌的保护作用，并探讨其与PI3K/Akt信号通路的关系。方法采用Langendorff系统灌注小鼠心脏，将其分为4组：1)含1 μmol/L S-equol （EQ）的改良Krebs-Henseleit （KH）缓冲液；2) KH缓冲液（Cont）；3) KH缓冲液中添加1 μmol/L S-equol和100 nmol/L wortmannin （PI3K特异性抑制剂）（EQW）；或4)含有wortmannin （ContW）的KH缓冲液。各组稳定后灌注20 min，无血流缺血7.5 min，再灌注20 min。主要终点是再灌注20分钟后的最大左心室压力发展导数（左心室[LV] dP/dt max）。western blotting检测心肌Akt和糖原合成酶激酶3β (GSK-3β)。结果再灌注15、20 min时，EQ组slv dP/dt max显著高于对照组；然而，这种作用在PI3K抑制剂的存在下减弱。与对照组相比，s -雌马酚处理增加了EQ组中Akt的表达，抑制了GSK-3β的表达。然而，在wortmannin存在的情况下，没有观察到这些影响。结论雌马酚可能通过激活PI3K/Akt信号通路，对心肌缺血再灌注损伤具有保护作用。

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

Steroids 医学-内分泌学与代谢

CiteScore

5.10

自引率

3.70%

发文量

120

审稿时长

73 days

期刊介绍： STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.