Potential therapeutic effect of curcumin, a natural mTOR inhibitor, in tuberous sclerosis complex

Phytomedicine. 2019 Feb 15:54:132-139. doi: 10.1016/j.phymed.2018.09.203. Epub 2018 Sep 20.


Background: Curcumin is a polyphenol natural product of the plant Curcuma longa. Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment.

Purpose: We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model.

Study design: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice.

Methods: The novel object recognition test was used to analyze the recognition memory function. The long-term potentiation was studied using electrophysiological analysis. Western blotting was used to assess the protein expression and activation status.

Results: Recognition memory deficit began as early as 4 weeks of age in both male and female Tsc2+/- mice. Oral administration with SLCP activates AMPK activity and inhibits mTOR activity in the brain tissue of Tsc2+/- mice, and can rescue the electrophysiological abnormality and object recognition memory loss in the mice.

Conclusions: Our results suggest that SLCP could be an effective treatment for TSC patients.

Keywords: Curcumin; Solid lipid curcumin particle; Tuberous sclerosis complex.

MeSH terms

  • Administration, Oral
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Female
  • Humans
  • Long-Term Potentiation / drug effects
  • Male
  • Memory Disorders / drug therapy
  • Mice, Knockout
  • Protein Kinase Inhibitors / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Tuberous Sclerosis / drug therapy*
  • Tuberous Sclerosis / metabolism
  • Tuberous Sclerosis Complex 2 Protein / genetics
  • Tuberous Sclerosis Complex 2 Protein / metabolism


  • Protein Kinase Inhibitors
  • Tsc2 protein, mouse
  • Tuberous Sclerosis Complex 2 Protein
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Curcumin