Ellagic acid attenuates muscle atrophy in STZ-induced diabetic mice

• Published in: Physiological research Vol. 71; no. 5; pp. 631 - 641
• Main Authors: Liu, X, Cheng, C, Deng, B, Liu, M
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 28.11.2022; Institute of Physiology of the Czech Academy of Sciences
• Subjects: Acids; Animals; Antibodies; Apoptosis; Atrophy; Bcl-2 protein; Cholesterol; Cholesterol - metabolism; Creatine; Creatine kinase; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Ellagic acid; Ellagic Acid - metabolism; Ellagic Acid - pharmacology; Ellagic Acid - therapeutic use; Endoplasmic reticulum; Glucose; High density lipoprotein; Homeostasis; Insulin; Kinases; L-Lactate dehydrogenase; Laboratory animals; Lactic acid; Lipids; Low density lipoprotein; Mice; Mitochondria; Morphology; Muscle, Skeletal - metabolism; Muscular Atrophy - drug therapy; Muscular Atrophy - metabolism; Muscular Atrophy - prevention & control; Musculoskeletal system; PGC-1 protein; Protein expression; Proteins; Regulation; Skeletal muscle; Streptozocin; Streptozocin - metabolism; Streptozocin - pharmacology; China
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.934918

Diabetes is closely connected with skeletal muscle dysfunction. Ellagic acid (EA) possesses a variety of bio-effects and is applied to the improvement of diabetes. The purpose of this study was to explore the potential improvement effect and mechanisms of EA in streptozotocin (STZ)-induced diabetic muscle atrophy. The model of diabetic mice was established by intra-peritoneal STZ to evaluate treatment effect of EA (100 mg/kg/d for 8 weeks) on muscle atrophy. Our data exhibited that EA enhanced fiber size and weight of gastrocnemius, and promoted grip strength to relieve STZ-induced muscle lesions. In serum, the levels of Creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) were inhibited, while high-density lipoprotein cholesterol (HDL) level was enhanced by EA treatment in diabetic mice. In gastrocnemius, EA decreased Atrogin-1 and MuRF-1 expressions to relieve STZ-induced muscle atrophy. Moreover, EA increased NRF-1 and PGC-1alpha expressions to alleviate mitochondrial disorder. Meanwhile, EA suppressed CHOP and GRP-87 levels to relieve ER stress. Lastly, EA inhibited BAX expressions and enhanced Bcl-2 expressions to mitigate apoptosis. In conclusion, EA is preventing the event of STZ-induced gastrocnemia by amelioration of mitochondrial dysfunction, ER stress and apoptosis, and could be used in the protection and therapeutic of muscle atrophy in diabetes.