Juzentaihoto Suppresses Muscle Atrophy in Streptozotocin-Induced Diabetic Mice

Biol Pharm Bull. 2019;42(7):1128-1133. doi: 10.1248/bpb.b18-00983.

Abstract

In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.

Keywords: diabetes; inflammatory; juzentaihoto; muscle atrophy.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Interleukin-10 / blood
  • Male
  • Mice, Inbred ICR
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins / genetics
  • Muscular Atrophy / blood
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / pathology
  • SKP Cullin F-Box Protein Ligases / genetics
  • Tripartite Motif Proteins / genetics
  • Tumor Necrosis Factor-alpha / blood
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Anti-Inflammatory Agents
  • Blood Glucose
  • Drugs, Chinese Herbal
  • IL10 protein, mouse
  • Muscle Proteins
  • Tnf protein, mouse
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha
  • juzentaihoto
  • Interleukin-10
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases