AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs

Eur J Pharmacol. 2015 Sep 5;762:299-305. doi: 10.1016/j.ejphar.2015.06.001. Epub 2015 Jun 3.

Abstract

AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties.

Keywords: AICAR; AMPK; Diclofenac; Ibuprofen; NSAID; Neuronal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line, Tumor
  • Diclofenac / pharmacology
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Ibuprofen / pharmacology
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Protein Subunits
  • Diclofenac
  • AMP-Activated Protein Kinases
  • Ibuprofen