Protective role of cichoriin and inulin against HFD-STZ-induced diabetic cardiomyopathy in mice via oxidative stress suppression and metabolic modulation

The distinctive characteristics of diabetic cardiomyopathy (DCM), a serious outcome of diabetes mellitus, are anomalies in the structure and functionality of the cardiac tissue. With a focus on their impact on inflammatory responses, oxidative injury, and the functioning of metabolic enzymes, this investigation aimed to evaluate the cardioprotective benefits of inulin and cichoriin over diabetes-related cardiomyopathy induced by high fat diet-streptozotocin (HFD-STZ) in mice. Diabetes was introduced in male Swiss albino mice by feeding them a high-fat diet followed by STZ injection and treated with cichoriin (50 and 100 mg/kg) or inulin (200 and 400 mg/kg). Serum biochemical, lipid, and cardiac injury markers were estimated. The metabolic enzyme activity (G6Pase, FBPase, ATPase, ENTPDase, 5'NT), oxidative stress markers (SOD, CAT, GSH, MDA, LDH), Angiotensin-Converting Enzyme (ACE) activity, and histological changes in the heart, pancreas, liver, and kidney, were assessed. NF-κB and Nrf2 immunohistochemistry was used to evaluate inflammatory and oxidative signalling. Treatment with inulin and cichoriin, especially at higher dosages, improved ACE activity, normalized metabolic enzyme activities, and substantially restored antioxidant enzyme levels. They reduced hyperglycemia, body weight loss, hyperlipidemia, and heart dysfunction with histological changes and fibrosis brought on by diabetes. Alongside these effects, cardiac tissues showed increased Nrf2 expression and decreased NF-κB, indicating the return of redox equilibrium and myocardial integrity. Thus, cichoriin and inulin substantially ameliorate the DCM by reducing oxidative injury, controlling glucose metabolism, and altering NF-κB/Nrf2 signaling pathways. These results demonstrate their potential for use as natural cardioprotective agents in the treatment of diabetic cardiomyopathy.