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Title

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

 

Authors

Muhammed Khairujjaman Mazumder & Anupom Borah*

 

Affiliation

Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar-788011, Assam, India

 

Email

anupomborahh@gmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received October 27, 2014; Accepted November 13, 2014; Published April 30, 2015

 

Abstract

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 of prostaglandins (PGs) and subsequently reactive oxygen species (ROS), aquaporin-4 (AQ-4) mediated brain edema and acid-sensing ion channel-1a (ASIC-1a) mediated acidotoxicity, matrix remodeling, in addition to others. Several non-steroidal anti-inflammatory drugs (NSAIDs) are presently in use to prevent these pathways. However, owing to the large number of processes involved, there is high drug load. So, identifying drugs with multimodal role has always been a frequently sought venture. The present in silico study has been performed to find out the relative efficacy of three different NSAIDs (Piroxicam, Aspirin and Nimesulide) in preventing neurodegeneration in CI, with respect to their inhibitory potential on COXs, AQ-4 and ASIC-1a. We find that piroxicam is the most potent inhibitor of these receptors as compared to the NSAIDs under investigation. Since piroxicam has already been reported to inhibit N-methyl-D-aspartate (NMDA) receptor and matrix metalloproteinases (MMPs), which are also linked to CI-induced neurodegeneration, we hereby propose piroxicam to be a gold-standard drug in preventing neurodegeneration in CI.

 

Keywords

ASIC-1a, aquaporin-4, COXs, inflammation, neuroprotection, non-steroidal anti-inflammatory drug, Piroxicam

 

Citation

Mazumder & Borah, Bioinformation 11(4): 217-222 (2015)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.