ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1621356
Cardioprotective Effects of Naringin in a Type 2 Diabetes Rodent Model by Reducing Calcium Overload and Oxidative Stress
Provisionally accepted
- 1Mount Sinai Medical Center, Miami Beach, United States
- 2Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela, Caracas, Venezuela
- 3Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, United States
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Abstract Introduction. 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 Ca²⁺ dyshomeostasis. Currently, there is no specific or effective treatment for DCM. Naringin (NRG), a flavonoid abundant in citrus fruits, has demonstrated promising cardioprotective properties. Methods. 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 four weeks to evaluate its cardioprotective efficacy in DCM. Results. Quiescent cardiomyocytes from db/db mice showed significantly increased diastolic Ca²⁺ levels ([Ca²⁺]d), 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 [Ca²⁺]d, 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. Conclusions. 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.
Keywords: cardiomyocytes, diabetes, Naringin, Calcium, Diabetic cardiomyopathy, Oxidative Stress
Received: 30 Apr 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Uryash, Mijares, Eltit, Adams and Lopez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jose R Lopez, Mount Sinai Medical Center, Miami Beach, United States
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