Prabhat, JagritiBashar, M. A.2025-06-192025-06-192025-03Prabhat Jagriti, Bashar M. A.. Indomethacin: A multifaceted therapeutic agent with potential applications. Indian Journal of Preventive and Social Medicine. 2025 Mar; 56(1): 51-630301-1216https://imsear.searo.who.int/handle/123456789/249997Background: 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.IndomethacinCyclooxygenase inhibitionCancer therapyAntiviral activityProstaglandin synthesisCytokine stormGastrointestinal toxicityTraumatic brain injuryPreterm laborPersonalized medicineDrug repurposingNonsteroidal anti-inflammatory drugs (NSAIDs).Journal ArticleIndiaAssociate Professor, Department of Biochemistry, All India Institute of Medical Sciences, Kunraghat, Gorakhpur, Uttar Pradesh: 273008, Email: drprabhat12811281@yahoo.in; Phone: 8318793132Ph.D. Student (Medical Biochemistry), Department of Biochemistry, All India Institute of Medical Sciences, Kunraghat, Gorakhpur, Uttar Pradesh: 273008, Email: jagsri43200@gmail.com; Mobile: 7379653599Assistant Professor, Department of Community and Family Medicine, All India Institute of Medical Sciences, Kunraghat, Gorakhpur, Uttar Pradesh: 273008, Email: imback20006@yahoo.in; Phone: 9501576052