Piroxicam confer neuroprotection in Cerebral Ischemia by inhibiting Cyclooxygenases,Acid- Sensing Ion Channel-1a and Aquaporin-4: an in silico comparison with Aspirin and Nimesulide

Cerebral ischemia (CI), caused by the deprivation of oxygen and glucose to the brain, is the leading cause of permanent disability.Neuronal demise in CI has been linked to several pathways which include cyclooxygenases (COX) − mediated production ofprostaglandins (PGs) and subsequently reactive oxygen species (ROS), aquaporin-4 (AQ-4) − mediated brain edema and acidsensingion channel-1a (ASIC-1a) − mediated acidotoxicity, matrix remodeling, in addition to others. Several non-steroidal antiinflammatorydrugs (NSAIDs) are presently in use to prevent these pathways. However, owing to the large number of processesinvolved, there is high drug load. So, identifying drugs with multimodal role has always been a frequently sought venture. Thepresent in silico study has been performed to find out the relative efficacy of three different NSAIDs (Piroxicam, Aspirin andNimesulide) in preventing neurodegeneration in CI, with respect to their inhibitory potential on COXs, AQ-4 and ASIC-1a. We findthat piroxicam is the most potent inhibitor of these receptors as compared to the NSAIDs under investigation. Since piroxicam hasalready been reported to inhibit N-methyl-D-aspartate (NMDA) receptor and matrix metalloproteinases (MMPs), which are alsolinked to CI-induced neurodegeneration, we hereby propose piroxicam to be a gold-standard drug in preventingneurodegeneration in CI.