Indomethacin: A multifaceted therapeutic agent with potential applications

Abstract

Background: Indomethacin, a well-established non-steroidal anti-inflammatory drug (NSAID), exhibits remarkable
therapeutic versatility across diverse medical applications. While traditionally recognized for its potent anti-inflammatory
and analgesic properties, recent studies underscore its potential in oncology, virology, neurology, and cardiovascular
health. Its primary mechanism involves cyclooxygenase (COX) inhibition, reducing prostaglandin synthesis, and
modulating immune responses. Beyond this, non-COX-mediated effects, such as autophagy regulation and mitochondrial
modulation, expand its therapeutic scope. Objective: This study aims to explore the broad therapeutic potential of
indomethacin beyond its conventional use as an anti-inflammatory agent, focusing on its applications in oncology,
virology, neurology, and other medical fields. Materials and Methods: A comprehensive review of preclinical and
clinical studies was conducted to evaluate the mechanisms, therapeutic benefits, and limitations of indomethacin.
Research findings on its role in cancer therapy, viral infections, neuroprotection, and inflammatory disorders were
analyzed, along with advancements in drug formulations to mitigate adverse effects. Results: Preclinical studies
demonstrate that Indomethacin restores apoptotic pathways by targeting anti-apoptotic Bcl-2 proteins, enhancing the
efficacy of immuno-therapies and chemotherapies in breast, colon, and prostate cancers. In vitro and clinical studies reveal
its dual antiviral action against SARS-CoV-2, canine coronavirus, and rotavirus, achieved by inhibiting viral replication
and suppressing cytokine storms. Clinical evidence highlights its ability to lower intracranial pressure (ICP) in traumatic
brain injury (TBI) and manage refractory migraines. Additionally, animal models suggest neuroprotective effects in
Alzheimer’s disease, including reduced amyloid-beta plaque formation. Furthermore, experimental studies validate its
potential to mitigate inflammation in rheumatoid arthritis and ankylosing spondylitis, while clinical trials in neonatology
confirm its efficacy in reducing intraventricular hemorrhage (IVH) severity. Conclusion: Despite its broad therapeutic
utility, indomethacin’s gastrointestinal (GI) toxicity remains a limitation. Advancements in drug formulations, including
phospholipid conjugates (e.g., DP-155), hydrogen sulfide-based derivatives, and nano-particles, have shown promise in
reducing adverse effects. Future research directions include large-scale clinical trials to validate its efficacy in under
explored therapeutic domains, mechanistic studies on non-COX pathways, and innovative combination therapies.
Indomethacin exemplifies the potential of repurposed drugs to address complex medical challenges. By leveraging its
restorative, synergistic, and multitargeted effects, alongside innovative delivery strategies, indomethacin can continue to
play a transformative role in modern medicine.