Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats

Int J Mol Sci. 2019 Oct 8;20(19):4955. doi: 10.3390/ijms20194955.

Abstract

Chrysanthemum boreale Makino essential oil (CBMEO) has diverse biological activities including a skin regenerating effect. However, its role in muscle atrophy remains unknown. This study explored the effects of CBMEO and its active ingredients on skeletal muscle atrophy using in vitro and in vivo models of muscle atrophy. CBMEO reversed the size decrease of L6 myoblasts under starvation. Among the eight monoterpene compounds of CBMEO without cytotoxicity for L6 cells, sabinene induced predominant recovery of reductions of myotube diameters under starvation. Sabinene diminished the elevated E3 ubiquitin ligase muscle ring-finger protein-1 (MuRF-1) expression and p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylations in starved myotubes. Moreover, sabinene decreased the increased level of reactive oxygen species (ROS) in myotubes under starvation. The ROS inhibitor antagonized expression of MuRF-1 and phosphorylation of MAPKs, which were elevated in starved myotubes. In addition, levels of muscle fiber atrophy and MuRF-1 expression in gastrocnemius from fasted rats were reduced after administration of sabinene. These findings demonstrate that sabinene, a bioactive component from CBMEO, may attenuate skeletal muscle atrophy by regulating the activation mechanism of ROS-mediated MAPK/MuRF-1 pathways in starved myotubes, probably leading to the reverse of reduced muscle fiber size in fasted rats.

Keywords: Chrysanthemum boreale Makino essential oil; L6 cells; MAPK/MuRF-1; sabinene; skeletal muscle atrophy.

MeSH terms

  • Animals
  • Bicyclic Monoterpenes / pharmacology*
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control*
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Tripartite Motif Proteins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Bicyclic Monoterpenes
  • Muscle Proteins
  • Reactive Oxygen Species
  • Tripartite Motif Proteins
  • sabinene
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases
  • Mitogen-Activated Protein Kinases