title: Neuroprotective and anti-apoptotic propensity of Bacopa monniera extract against sodium nitroprusside induced activation of iNOS, heat shock proteins and apoptotic markers in PC12 cells.
abstract: Sodium nitroprusside (SNP) is a widely used nitric oxide (NO) donor, known to exert nitrative stress by up-regulation of inducible nitric oxide synthase (iNOS). Nω-nitro-L-arginine-methyl esther (L-NAME) is a NO inhibitor, which inhibits iNOS expression, is used as positive control. The present study was designed to assess neuroprotective propensity of Bacopa monniera extract (BME) in SNP-induced neuronal damage and oxido-nitrative stress in PC12 cells via modulation of iNOS, heat shock proteins and apoptotic markers. Our results elucidate that pre-treatment of PC12 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP (200 μM) as evidenced by MTT and LDH assays. BME pre-treatment inhibited NO generation by down regulating iNOS expression. BME replenished the depleted antioxidant status induced by SNP treatment. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic protein biomarkers such as Bax, Bcl-2, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. Q-PCR results further elucidated up-regulation of neuronal cell stress markers like HO-1 and iNOS and down-regulation of BDNF upon SNP exposure was attenuated by BME pre-treatment. By considering all these findings, we report that BME protects PC12 cells against SNP-induced toxicity via its free radical scavenging and neuroprotective mechanism.
authors.affiliation: Biochemistry and Nanosciences Discipline, Defence Food Research Laboratory, Siddarthanagar, 570011, Mysore, India.
authors.forename: M D
authors.initials: MD
authors.lastname: Pandareesh
authors.forename: T
authors.initials: T
authors.lastname: Anand
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D034681:Bacopa / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats
chemical_list: D010936:Plant Extracts; D009599:Nitroprusside; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester