Ampelopsin attenuates the atrophy of skeletal muscle from d-gal-induced aging rats through activating AMPK/SIRT1/PGC-1α signaling cascade

Biomed Pharmacother. 2017 Jun:90:311-320. doi: 10.1016/j.biopha.2017.03.070. Epub 2017 Mar 30.

Abstract

The atrophy of skeletal muscle is highly correlated with oxidative damage, excessive apoptosis and dysfunctional autophagy. Ampelopsin, a natural flavonoid, has multiple biological functions including anti-inflammatory, anti-oxidative, and hepatoprotective functions. Sprague-Dawley (SD) rats subjected to intraperitoneal injection of d-galactose (d-gal) at the dose of 150mg/kg·d revealed an obvious atrophy of skeletal muscle with significantly reduced muscle mass/body mass ratio, cross-sectional area and fiber diameter of skeletal muscle in d-gal-induced aging rats when compared to normal control rats without d-gal administration for 6 consecutive weeks. In contrast, the combinatorial administration of d-gal at the identical dose and DHM at the dose of 100 or 200mg/kg·d could alleviate the reduction of these hallmarks associated with the atrophy of skeletal muscle. In addition, d-gal administration could result in obvious apoptosis and impaired autophagy in skeletal muscle, which could be mitigated upon DHM treatment due to its role in decreasing ubiquitin and Atrogin-1/MAFbx and up-regulating AMPK and SIRT1 signal pathways. Therefore, DHM may be a potential candidate for the prevention and treatment of skeletal muscle atrophy associated aging process.

Keywords: Ampelopsin; Autophagy; Skeletal muscle atrophy; d-Galactose; p-AMPK-PGC-1α signal pathway.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Flavonoids / pharmacology*
  • Galactose / pharmacology
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / chemically induced
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Sirtuin 1 / metabolism*
  • Up-Regulation / drug effects

Substances

  • Flavonoids
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • ampelopsin
  • AMP-Activated Protein Kinases
  • Sirt1 protein, rat
  • Sirtuin 1
  • Galactose