clovamide and Disease-Models--Animal

A series of clovamide analogues, namely, 1a-13a and 1b-13b, was synthesized and evaluated for their anti-neuroinflammatory activities using BV-2 microglia cells. Among these compounds, six (1b, 4b-8b) showed NO inhibition with no or weak cytotoxicity (CC

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Anti-Inflammatory Agents; Cell Line; Disease Models, Animal; Humans; Male; Mice, Inbred C57BL; Molecular Docking Simulation; Neuroprotective Agents; Nitric Oxide Synthase Type II; Parkinson Disease, Secondary; Tyrosine

Neuroinflammation is one of the critical pathological mechanisms influencing various neurodegenerative disorders. Most of the neurodegenerative diseases involve over-activation of microglial cells contributing to the demise of neurons. The objective of the current study is to evaluate the anti-inflammatory effect of novel synthetic clovamide derivative on the suppression of microglial activation in an in vitro and in vivo model of neuroinflammation. We have used lipopolysaccharide (LPS) to induce an inflammatory response in murine BV-2 microglial cells. Molecular tools like immunocytochemistry and immunoblotting were used to study the activity of novel synthetic clovamide derivative to inhibit inflammation induced by LPS in microglial cells. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of neuroinflammation was developed to investigate the anti-neuroinflammatory effects of DPTP [3-(3,4-Dihydroxy-phenyl)-2-[4-(3-trifluoromethylphenyl)-but-2-enoylamino]-propionic acid methyl ester]. DPTP was observed to reduce the proinflammatory response in BV-2 cells induced by LPS. Further investigation revealed that DPTP attenuated phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which was accompanied by a decrease in nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 microglia. Moreover, prophylactic treatment with DPTP (20mg/kg) for 7 days suppressed MPTP induced glial activation and behavioral impairment. Overall, our findings suggested that, DPTP exerts anti-neuroinflammatory effects against activated microglia in an in vitro and in vivo model and hence might be a promising therapeutic agent for alleviating the evolvement of neurodegenerative diseases associated with microglial activation.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Brain; Cell Line; Cells, Cultured; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Inflammation; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroimmunomodulation; Neuroprotective Agents; NF-kappa B; Phosphorylation; Rats, Sprague-Dawley; Tyrosine