Alpha-lipoic acid: A promising adjuvant for nonsteroidal anti-inflammatory drugs therapy with improved efficacy and gastroprotection

Drug Dev Res. 2021 Sep;82(6):844-851. doi: 10.1002/ddr.21791. Epub 2021 Jan 24.


Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in a wide variety of diseases due to their analgesic and anti-inflammatory effects, but their usage have been limited due to significant ulcerogenic side effects. In the present study, we aimed to evaluate the effect of α-lipoic acid (ALA) treatment on the anti-inflammatory activity of indomethacin (Indo) as well as the possible therapeutic effect of ALA on high dose Indo-induced gastropathy in female mice. Mice were treated with Indo (5 or 30 mg/kg, p.o) alone or in combination with ALA (50, 100 or 200 mg/kg, i.p). in vivo anti-inflammatory effect was evaluated by formalin-induced paw edema measured as paw thickness and edema. Gastric damage was evaluated macroscopically and histologically by scoring mucosal hemorrhage, erosion, edema and inflammation. To our results, Indo was ineffective at 5 mg/kg, but co-treatment with Indo and ALA significantly reduced paw edema, implying that ALA augmented the anti-inflammatory effect of subtherapeutic dose of Indo. However, ALA was not able to induce a further increase in the anti-inflammatory effect of Indo at 30 mg/kg. Unlike the treatment with Indo at 5 mg/kg, Indo at 30 mg/kg caused severe gastric damage that prevented by co-treatment with ALA. These results suggest that combination of ALA with NSAIDs can both increase anti-inflammatory effect and prevent NSAIDs-induced gastric damage. ALA would be promising adjuvant that can reduce dose for effective NSAID therapy, which improves safety profile of NSAIDs especially in cases long-term administration of high dose needed.

Keywords: alpha lipoic acid; anti-inflammatory; gastric damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Female
  • Gastric Mucosa
  • Indomethacin / adverse effects
  • Mice
  • Thioctic Acid* / pharmacology
  • Thioctic Acid* / therapeutic use


  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Thioctic Acid
  • Indomethacin