The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6

• Published in: Chemico-biological interactions 2012-12, Vol.200 (2-3), p.73-83
• Main Authors: Niranjan, Rituraj, N, Rajasekar, Nath, Chandishwar, Shukla, Rakesh
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; antioxidant activity; astrocytes; Astrocytoma - pathology; Base Sequence; calcium; Cell Line, Tumor; Cyclooxygenase 2 - genetics; Cytokines - genetics; Cytokines - metabolism; cytosol; DNA Primers; drugs; gene expression regulation; genes; Guggulipid and nimesulide; inducible nitric oxide synthase; Inflammation Mediators - metabolism; interleukin-1beta; interleukin-6; messenger RNA; mitogen-activated protein kinase; MPTP; necrosis; Nervous System - pathology; Neuroinflammation; NF-κB activation; Nitric Oxide Synthase Type II - metabolism; oxidative stress; p38 Mitogen-Activated Protein Kinases - metabolism; Parkinson disease; pathophysiology; Phosphorylation; Plant Extracts - pharmacology; Plant Gums - pharmacology; prostaglandin synthase; Rat astrocytoma cells (C6); Rats; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides - pharmacology; transcription (genetics); Transcription Factor CHOP - metabolism; transcription factor NF-kappa B; tumor necrosis factor-alpha
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2012.08.008

► Oxidative stress is involved in activation of astroglial, C6 cells. ► Guggulipid showed protective effects against MPTP stimulated astroglial cells. ► Both nimesulide and guggulipid inhibited intracellular calcium ion. ► NF-κB and CHOP activation are inhibited by these drugs. ► Pro-inflammatory cytokine mRNA expressions are reversed by these drugs. 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 24h significantly decreased MPTP (400μM) induced nitrative and oxidative stress and intracellular calcium ion (Ca2+) 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.