Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach

J Enzyme Inhib Med Chem. 2019 Dec;34(1):927-936. doi: 10.1080/14756366.2019.1596904.

Abstract

Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (-4.6 kcal/mol), elastase (-3.36 kcal/mol) and tyrosinase (-2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively.

Keywords: Caffeine; enzyme inhibition; matrix metalloproteinases; molecular docking; photoageing.

MeSH terms

  • Agaricus / enzymology
  • Animals
  • Caffeine / chemistry
  • Caffeine / pharmacology*
  • Clostridium histolyticum / enzymology
  • Collagenases / metabolism*
  • Computer Simulation*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • In Vitro Techniques
  • Ligands
  • Molecular Dynamics Simulation
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Pancreas / enzymology
  • Pancreatic Elastase / antagonists & inhibitors*
  • Pancreatic Elastase / metabolism
  • Structure-Activity Relationship
  • Swine

Substances

  • Enzyme Inhibitors
  • Ligands
  • Caffeine
  • Monophenol Monooxygenase
  • Pancreatic Elastase
  • Collagenases

Grants and funding

This work was supported by the Yeungnam University Research Grant (214A345038).