Department of Biochemistry, Centre for Excellence in Genomics Science, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, 625 021, India.
Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, USA.
Mol Cell Biochem. 2021 Jul;476(7):2719-2727. doi: 10.1007/s11010-021-04105-5. Epub 2021 Mar 7.
Hypercholesterolemia is one of the risk factors associated with increased morbidity and mortality in cardiovascular disorders. Chrysin (Chy) is reported to exhibit anti-inflammatory, anti-cancerous, anti-oxidative, anti-aging, and anti-atherogenic properties. In the present study, we aimed to investigate whether Chy would mediate the cardioprotective effect against hypercholesterolemia-triggered myocardial oxidative stress. Male Sprague Dawley rats were divided into different groups as control and fed with high-fat diet (HFD) followed by oral administration of Chy (100 mg/kg b.wt), atorvastatin (Atv) (10 mg/kg b.wt), and L-NAME (10 mg/kg b.wt) for 30 days. At the end of the experimental period, the rats were sacrificed and tissues were harvested. Biochemical results showed a significant increase of cardiac disease marker enzymes (ALT, AST, and CKMB), lipid peroxidation, and lipid profile (TC, TG, LDL, and VLDL) in HFD-fed rat tissues when compared to control, whereas oral administration of Chy significantly reduced the activities of these marker enzymes and controlled the lipid profile. qRT-PCR studies revealed that Chy administration significantly increased the expression of endothelial nitric oxide synthase (eNOS), and Nrf2 target genes such as SOD, catalase, and GCL3 in left ventricular heart tissue of HFD-challenged rats. Immunohistochemistry results also showed that Chy treatment increased myocardial protein expression of eNOS and Nrf2 in HFD-challenged rats. Concluding the results of the present study, the Chy could mediate the cardioprotective effect through the activation of eNOS and Nrf2 signaling against hypercholesterolemia-induced oxidative stress. Thus, the administration of Chy would provide a promising therapeutic strategy for the prevention of HFD-induced oxidative stress-mediated myocardial complications.
高胆固醇血症是心血管疾病发病率和死亡率增加的相关风险因素之一。白杨素（Chy）具有抗炎、抗癌、抗氧化、抗衰老和抗动脉粥样硬化作用。在本研究中，我们旨在研究白杨素是否会介导对高胆固醇血症引发的心肌氧化应激的心脏保护作用。雄性 Sprague Dawley 大鼠分为对照组和高脂饮食（HFD）组，随后 HFD 组大鼠口服给予白杨素（100mg/kg 体重）、阿托伐他汀（Atv）（10mg/kg 体重）和 L-NAME（10mg/kg 体重）30 天。实验结束时，处死大鼠并采集组织。生化结果显示，与对照组相比，HFD 喂养的大鼠组织中心脏病标志物酶（ALT、AST 和 CKMB）、脂质过氧化和脂质谱（TC、TG、LDL 和 VLDL）显著增加，而白杨素口服给药可显著降低这些标志物酶的活性并控制脂质谱。qRT-PCR 研究表明，白杨素给药可显著增加 HFD challenged 大鼠左心室心肌中内皮型一氧化氮合酶（eNOS）和 Nrf2 靶基因（如 SOD、过氧化氢酶和 GCL3）的表达。免疫组织化学结果还表明，白杨素处理可增加 HFD challenged 大鼠心肌中 eNOS 和 Nrf2 的蛋白表达。综上所述，本研究结果表明，白杨素可通过激活 eNOS 和 Nrf2 信号通路来介导对高胆固醇血症诱导的氧化应激的心脏保护作用。因此，白杨素的给药可能为预防 HFD 诱导的氧化应激介导的心肌并发症提供一种有前景的治疗策略。
