title: The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6.
abstract: Oxidative stress plays an important role in the pathophysiology of Parkinson's disease (PD) but its mechanism is still not properly explored. Cyclooxygenase-2 (COX-2) inhibition has also been known a major neuroprotective strategy in the various 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induced models of Parkinson's disease (PD) but its role in astrocytes is still not properly understood. The present study demonstrated that, guggulipid and nimesulide (preferentially selective COX-2 inhibitor) treatment of rat astrocytoma cells, C6 for 24 h significantly decreased MPTP (400 μM) induced nitrative and oxidative stress and intracellular calcium ion (Ca(2+)) level. Guggulipid and nimesulide also deactivated MPTP-induced P-p38 MAPK (Phosphorylated p38 mitogen-activated protein kinase) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and CHOP (C/EBP, homologous protein 10). At transcriptional level of inflammatory cytokine genes, guggulipid and nimesulide down regulated MPTP-induced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA expressions with up regulations in interleukin-6 (IL-6) and interleukin-1α (IL-1α) mRNA expressions. In addition to this, guggulipid and nimesulide inhibited translocation of nuclear factor kappa-B (NF-κB) from cytosol to nucleus. In conclusion, our findings elucidated the potential antioxidant and anti-neuroinflammatory effect of guggulipid and nimesulide in rat astrocytoma cells C6, which may suggest the use of these drugs in the management of neuroinflammation associated pathophysiology of PD.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow 226001, UP, India.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Niranjan
authors.forename: N
authors.initials: N
authors.lastname: Rajasekar
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
authors.forename: Rakesh
authors.initials: R
authors.lastname: Shukla
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001254:Astrocytoma / Q000473:pathology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D029744:Commiphora; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D018836:Inflammation Mediators / Q000378:metabolism*; D009420:Nervous System / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D053149:Plant Gums / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D017931:DNA Primers; C497251:Ddit3 protein, rat; D018836:Inflammation Mediators; D010936:Plant Extracts; D053149:Plant Gums; D013449:Sulfonamides; D051742:Transcription Factor CHOP; C018562:guggulu extract; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; C012655:nimesulide