Schisandrae chinensis Fructus Extract Ameliorates Muscle Atrophy in Streptozotocin-Induced Diabetic Mice by Downregulation of the CREB-KLF15 and Autophagy–Lysosomal Pathways

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 9; p. 2283
• Main Authors: Choi, Ho-Jung, Yeon, Myeong-Hoon, Jun, Hee-Sook
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 02.09.2021; MDPI
• Subjects: Antibodies; Atrophy; Autoimmune diseases; Autophagy; Beta cells; Blood glucose; Cyclic AMP response element-binding protein; Diabetes; Diabetes mellitus (insulin dependent); Gastrocnemius muscle; Glucose; Hyperglycemia; Insulin; Laboratory animals; Medical research; muscle protein degradation; muscle wasting; Musculoskeletal system; Oral administration; Phagocytosis; Protein synthesis; Proteins; Quality of life; Schisandrae chinensis Fructus; Skeletal muscle; Streptozocin; streptozotocin-induced diabetic mice; St Louis Missouri; United States > US; Japan
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10092283

Type 1 diabetes mellitus is an autoimmune disease caused by the destruction of pancreatic beta cells. Many patients with type 1 diabetes experience skeletal muscle wasting. Although the link between type 1 diabetes and muscle wasting is not clearly known, insulin insufficiency and hyperglycemia may contribute to decreased muscle mass. In this study, we investigated the therapeutic effect of the ethanolic extract of Schisandrae chinensis Fructus (SFe) on muscle wasting in streptozotocin (STZ)-induced diabetic mice. STZ-diabetic C57BL/6 mice (blood glucose level ≥300 mg/dL) were orally administered SFe (250 or 500 mg/kg/day) for 6 weeks. We observed that SFe administration did not change blood glucose levels but increased gastrocnemius muscle weight, cross-sectional area, and grip strength in STZ-induced diabetic mice. Administration of SFe (500 mg/kg) decreased the expression of atrophic factors, such as MuRF1 and atrogin-1, but did not alter the expression of muscle synthetic factors. Further studies showed that SFe administration decreased the expression of KLF15 and p-CREB, which are upstream molecules of atrophic factors. Examination of the expression of molecules involved in autophagy–lysosomal pathways (e.g., p62/SQSTM1, Atg7, Beclin-1, ULK-1, LC3-I, and LC3-II) revealed that SFe administration significantly decreased the expression of p62/SQSTM1, LC3-I, and LC3-II; however, no changes were observed in the expression of Atg7, Beclin-1, or ULK-1. Our results suggest that SFe ameliorated muscle wasting in STZ-induced diabetic mice by decreasing protein degradation via downregulation of the CREB-KLF15-mediated UPS system and the p62/SQSTM1-mediated autophagy–lysosomal pathway.