Chen JH, Dai XC, Quan ZJ, Liu XY. Erianin mitigates diabetic cardiomyopathy via adenosine monophosphate-activated protein kinase-nuclear factor erythroid 2-related factor 2-heme oxygenase-1 pathway activation. World J Diabetes 2025; 16(6): 103685 [DOI: 10.4239/wjd.v16.i6.103685]
Corresponding Author of This Article
Xin-Yu Liu, PhD, Professor, Department of Gerontology, The First Affiliated Hospital of Jinzhou Medical University, No. 2 Section 5, Renmin Street, Guta District, Jinzhou 121012, Liaoning Province, China. lxy20240520@163.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jun 15, 2025; 16(6): 103685 Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.103685
Erianin mitigates diabetic cardiomyopathy via adenosine monophosphate-activated protein kinase-nuclear factor erythroid 2-related factor 2-heme oxygenase-1 pathway activation
Jia-Hui Chen, Xiao-Chun Dai, Zi-Jiao Quan, Xin-Yu Liu
Jia-Hui Chen, Xin-Yu Liu, Department of Gerontology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121012, Liaoning Province, China
Jia-Hui Chen, Xiao-Chun Dai, Department of Gerontology, The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou 325000, Zhejiang Province, China
Zi-Jiao Quan, College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, Zhejiang Province, China
Author contributions: Chen JH and Liu XY designed the experiments, conducted clinical data collection, conducted the collation, statistical analysis, and wrote the original manuscript and revised the paper; Dai XC and Quan ZJ performed postoperative follow-up and recorded the data; All authors read and approved the final manuscript.
Institutional animal care and use committee statement: All experimental procedures were approved by the Animal Ethics Committee of Jinzhou Medical University (No. 2023062) and conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xin-Yu Liu, PhD, Professor, Department of Gerontology, The First Affiliated Hospital of Jinzhou Medical University, No. 2 Section 5, Renmin Street, Guta District, Jinzhou 121012, Liaoning Province, China. lxy20240520@163.com
Received: December 20, 2024 Revised: March 21, 2025 Accepted: April 17, 2025 Published online: June 15, 2025 Processing time: 175 Days and 3.9 Hours
Abstract
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.
Core Tip: This study investigates the cardioprotective effects of erianin, a natural compound from Dendrobium chrysotoxum, in a type 2 diabetic mouse model. Erianin administration significantly reduced myocardial damage and improved metabolic parameters by activating the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. These findings suggest that erianin may serve as a potential therapeutic agent to mitigate cardiac injury and inflammation in diabetes, offering new insights into managing diabetic cardiomyopathy.
