Oligonol, a Low-Molecular Weight Polyphenol Derived from Lychee, Alleviates Muscle Loss in Diabetes by Suppressing Atrogin-1 and MuRF1

Nutrients. 2017 Sep 20;9(9):1040. doi: 10.3390/nu9091040.


Stimulation of the ubiquitin-proteasome pathway-especially E3 ubiquitin ligases Atrogin-1 and MuRF1-is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks) oligonol supplementation (20 or 200 mg/kg diet) on the skeletal muscle loss was investigated in diabetic db/db mice. Transcription factors NF-κB and FoxO3a involved in regulation of Atrogin-1 and MuRF1 were also investigated. Attenuation of muscle loss by oligonol (both doses) was associated with down-regulation of Atrogin-1 and MuRF1 gene expression. Oligonol supplementation decreased NF-κB expression in the nuclear fraction compared with db/db mice without oligonol supplement. Upregulation of sirtuin1 (SIRT1) expression prevented FoxO3a nuclear localization in db/db mice supplemented with oligonol. Marked increases in AMPKα activity and Ppara mRNA expression leading to lower lipid accumulation by oligonol provided additional benefits for attenuating muscle loss. Oligonol limited palmitate-induced senescent phenotype and cell cycle arrest and suppressed Atrogin-1 and MuRF1 mRNA expression in palmitate-treated C2C12 muscle cells, thus contributing to improving the impaired myotube formation. In conclusion, oligonol-mediated downregulation of Atrogin-1 and MuRF1 gene expression alleviates muscle loss and improves the impaired myotube formation, indicating that oligonol supplementation may be useful for the attenuation of myotube loss.

Keywords: Atrogin-1 and MuRF1; NF-κB; diabetes; flavanol-rich lychee fruit extract; muscle loss.

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism
  • Fruit / chemistry
  • Gene Expression Regulation
  • Litchi / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Weight
  • Muscle Proteins / antagonists & inhibitors*
  • Muscle Proteins / genetics
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phenols / pharmacology*
  • Polyphenols / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases / antagonists & inhibitors*
  • SKP Cullin F-Box Protein Ligases / genetics
  • Sarcopenia / drug therapy*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Tripartite Motif Proteins / antagonists & inhibitors*
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / genetics


  • Forkhead Box Protein O3
  • FoxO3 protein, mouse
  • Muscle Proteins
  • NF-kappa B
  • Phenols
  • Polyphenols
  • RNA, Messenger
  • Tripartite Motif Proteins
  • oligonol
  • Catechin
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • Sirt1 protein, mouse
  • Sirtuin 1