Erianin mitigates diabetic cardiomyopathy via adenosine monophosphate-activated protein kinase-nuclear factor erythroid 2-related factor 2-heme oxygenase-1 pathway activation.

BACKGROUND: Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties. AIM: To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes. METHODS: High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice. Mice were divided into different groups including control, model, and treatment with various doses of erianin (10, 20, and 40 mg/kg) as well as ML-385 + erianin group. RESULTS: Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) pathway. Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls. Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function (left ventricular ejection fraction, left ventricular fractional shortening) and mitigated ventricular remodeling (left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole; P < 0.05 vs model group). No significant differences were observed between the ML-385 + erianin and placebo-treated groups. Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation, structural disorganization, inflammatory cell infiltration, and cytolytic damage. Furthermore, it significantly reduced the serum levels of cardiac troponin I, creatine kinase, and its MB isoenzyme. However, the ML-385 + erianin co-treatment failed to alleviate myocardial injury. Metabolic profiling revealed erianin-mediated improvements in glycemic regulation (glycated hemoglobin: P < 0.001), plasma insulin homeostasis, and lipid metabolism (total cholesterol, triglycerides, low-density lipoprotein cholesterol reduction, and high-density lipoprotein cholesterol restoration; P < 0.05 vs model group). Proinflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group, whereas no significant differences were detected between the model and ML-385 + erianin groups. Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups, with the most pronounced effects in the erianin-H group (P < 0.05). Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups. These protective effects were abolished in the ML-385 + erianin co-treatment group, which showed no statistical differences from the model group. CONCLUSION: Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.