Diabetic cardiomyopathy (DCM), a diabetes complication, accounts for diabetes-associated morbidity, mortality, and heart failure. Biflavonoids have been demonstrated to possess extensive pharmacological properties, such as antidiabetic and antioxidant activities. Our study aimed to explore the effects of sciadopitysin, a type of biflavonoid, on DCM and the mechanism involved. An experimental cell model was established in AC16 cardiomyocytes by exposure to high glucose (HG). Cell injury was estimated by detecting cell viability and lactate dehydrogenase (LDH) release. Oxidative stress was determined by measuring malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Apoptosis was assessed by flow cytometry analysis, caspase-3/7 activity assay, and Western blot analysis of cytochrome C (Cyt C) expression. Alternation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3β (GSK-3β) pathway was detected by Western blot. Results showed that HG exposure reduced viability and increased LDH release in AC16 cells, which was abolished by sciadopitysin treatment. Sciadopitysin inhibited HG-induced oxidative stress, as evidenced by the reduced MDA content, and the increased activities of SOD, CAT, and GSH-Px. Sciadopitysin suppressed HG-induced apoptosis, an increase of caspase-3/7 activity, and Cyt C expression in AC16 cells. Mechanistically, sciadopitysin activated the PI3K/PKB/GSK-3β pathway under HG stimulation in AC16 cells. Inhibition of PI3K/PKB/GSK-3β pathway by LY294002 blocked the effects of sciadopitysin on HG-induced injury, oxidative stress, and apoptosis in AC16 cells. Summarily, sciadopitysin alleviated HG-caused oxidative stress and apoptosis in cardiomyocytes by activating the PI3K/PKB/GSK-3β pathway.

中文翻译：

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sciadopitysin 激活 PI3K/PKB/GSK-3β 信号通路保护心肌细胞免受高糖诱导的氧化应激和细胞凋亡

糖尿病性心肌病 (DCM) 是一种糖尿病并发症，可导致糖尿病相关的发病率、死亡率和心力衰竭。双黄酮类化合物已被证明具有广泛的药理特性，例如抗糖尿病和抗氧化活性。我们的研究旨在探索 sciadopitysin（一种双黄酮类化合物）对 DCM 的影响及其相关机制。通过暴露于高葡萄糖 (HG) 在 AC16 心肌细胞中建立实验细胞模型。通过检测细胞活力和乳酸脱氢酶 (LDH) 释放来估计细胞损伤。通过测量丙二醛 (MDA) 水平和超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH-Px) 和过氧化氢酶 (CAT) 的活性来确定氧化应激。通过流式细胞术分析、caspase-3/7 活性测定、和蛋白质印迹分析细胞色素 C (Cyt C) 的表达。磷脂酰肌醇 3 激酶 (PI3K)/蛋白激酶 B (PKB)/糖原合酶激酶 3 的交替通过蛋白质印迹检测β（GSK- 3β ）途径。结果表明，HG 暴露降低了 AC16 细胞的活力并增加了 LDH 的释放，而这被 sciadopitysin 处理所消除。Sciadopitysin 抑制 HG 诱导的氧化应激，这可以通过降低 MDA 含量和增加 SOD、CAT 和 GSH-Px 的活性来证明。Sciadopitysin 抑制 HG 诱导的细胞凋亡、caspase-3/7 活性的增加和 AC16 细胞中 Cyt C 的表达。机制上，sciadopitysin在 HG 刺激下激活 AC16 细胞中的 PI3K/PKB/GSK-3 β通路。抑制 PI3K/PKB/GSK-3 βLY294002 的通路阻断了 sciadopitysin 对 HG 诱导的 AC16 细胞损伤、氧化应激和凋亡的影响。总之，sciadopitysin 通过激活 PI3K/PKB/GSK-3 β通路减轻 HG 引起的心肌细胞氧化应激和凋亡。