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

• Published in: Neurochemical research Vol. 39; no. 5; pp. 800 - 814
• Main Authors: Pandareesh, M. D., Anand, T.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2014; Springer Nature B.V
• Subjects: Animals; Apoptosis - drug effects; Bacopa - chemistry; Bacopa monniera; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Down-Regulation - drug effects; Neurochemistry; Neurology; Neurosciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitroprusside - pharmacology; Original Paper; Oxidative Stress - drug effects; PC12 Cells; Plant Extracts - therapeutic use; Rats; Inducible nitric oxide synthase (iNOS); Sodium nitroprusside; Nitric oxide; PC12 cells; Apoptosis
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-014-1273-7

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.