Piperine reported to have diverse pharmacological potentials has been screened towards a number of anti-inflammatory molecular targets such as Cox-2, interleukin-1β (IL-1β), IL-4, IL-13, matrix metallopeptidase-3 (MMP-3), MMP-8
in-silico using the various computational tools like variable nearest neighbour absorption, distribution, metabolism, excretion, and toxicity (vNN-ADMET), SWISS ADME, Spartan-14, iGemdock, and DS-Visualizer. The results when compared with commercial drugs exhibited parallel anti-inflammatory potential with ibuprofen and naproxen. In addition, we here report in-vitro anti-cathepsin B and serum protein-protecting activities. Complete inhibition of cathepsin B was observed at 200 µM of piperine and 250 µM for both indomethacin and naproxen, respectively. And, 100% anti-denaturation was observed at 10 µM of piperine, and 15 µM of indomethacin and naproxen. The results validated the anti-inflammatory potential of piperine, with both in silico and in vitro studies targeting previously unreported mechanisms.