Uryash Arkady, Mijares Alfredo, Eltit Jose Miguel, Adams Jose A, Lopez Jose R
Division of Neonatology, Mount Sinai Medical Center, Miami, FL, United States.
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Front Pharmacol. 2025 Aug 6;16:1621356. doi: 10.3389/fphar.2025.1621356. eCollection 2025.
Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations in the heart muscle, occurring independently of other cardiovascular risk factors such as dyslipidemia, hypertension, or coronary artery disease. Despite efforts to manage type 2 diabetes (T2D) and its complications, DCM remains a significant cause of morbidity and mortality in diabetic patients. The pathogenesis of DCM is multifactorial, involving oxidative stress, inflammation, and intracellular Ca dyshomeostasis. Currently, there is no specific or effective treatment for DCM. Naringin (NRG), a flavonoid abundant in citrus fruits, has demonstrated promising cardioprotective properties.
Cardiomyocytes were isolated from a 12-month-old murine T2D model (db/db mice) and corresponding age-matched control subjects. Naringin was administered via intraperitoneal injection at a dosage of 60 mg/kg for 4 weeks to evaluate its cardioprotective efficacy in DCM.
Quiescent cardiomyocytes from db/db mice showed significantly increased diastolic Ca levels ([Ca]), reactive oxygen species (ROS), lipid peroxidation, advanced oxidation protein products (AOPP), and nicotinamide adenine dinucleotide phosphate (NADPH) levels, along with reduced superoxide dismutase (SOD) activity and adiponectin (APN) levels. Plasma markers of cardiac injury were also elevated compared to those in the control group. NRG treatment significantly reduced [Ca], ROS, lipid peroxidation, AOPP, and NADPH levels while enhancing SOD activity and APN levels. Furthermore, NRG attenuated plasma cardiac injury markers in db/db mice.
The results of this study illustrate the cardioprotective potential of NRG in diabetic cardiomyopathy by mitigating intracellular calcium overload and oxidative stress, augmenting antioxidant defenses, and reducing cardiac injury. NRG could serve as a promising adjunctive therapeutic approach to enhance cardiac function in diabetic patients.
糖尿病性心肌病（DCM）的特征是心肌出现结构和功能改变，其发生独立于其他心血管危险因素，如血脂异常、高血压或冠状动脉疾病。尽管人们努力控制2型糖尿病（T2D）及其并发症，但DCM仍然是糖尿病患者发病和死亡的重要原因。DCM的发病机制是多因素的，涉及氧化应激、炎症和细胞内钙稳态失衡。目前，尚无针对DCM的特异性或有效治疗方法。柚皮苷（NRG）是柑橘类水果中富含的一种黄酮类化合物，已显示出有前景的心脏保护特性。
从12月龄的小鼠T2D模型（db/db小鼠）和相应年龄匹配的对照小鼠中分离心肌细胞。以60mg/kg的剂量通过腹腔注射给予柚皮苷4周，以评估其对DCM的心脏保护作用。
db/db小鼠的静止心肌细胞显示舒张期钙水平（[Ca]）、活性氧（ROS）、脂质过氧化、晚期氧化蛋白产物（AOPP）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）水平显著升高，同时超氧化物歧化酶（SOD）活性和脂联素（APN）水平降低。与对照组相比，心脏损伤的血浆标志物也升高。NRG治疗显著降低了[Ca]、ROS、脂质过氧化、AOPP和NADPH水平，同时增强了SOD活性和APN水平。此外，NRG减轻了db/db小鼠的血浆心脏损伤标志物。
本研究结果表明，NRG通过减轻细胞内钙超载和氧化应激、增强抗氧化防御以及减少心脏损伤，在糖尿病性心肌病中具有心脏保护潜力。NRG可作为一种有前景的辅助治疗方法来增强糖尿病患者的心脏功能。
