title: Neuroprotective mechanisms of the standardized extract of Bacopa monniera in a paraquat/diquat-mediated acute toxicity.
abstract: Parkinson's disease (PD) is one of the most common age related neurodegenerative disease and affects millions of people worldwide. Strong evidence suggests a role for oxidative stress and mitochondrial dysfunctions in the pathogenesis of PD. Recent epidemiologic and toxicological studies have shown that environmental factors, especially herbicides such as paraquat and diquat represent one of the primary classes of neurotoxic agents associated with PD. The objective of our study was to investigate the neuroprotective effects of the standardized extract of Bacopa monniera (BM) against paraquat/diquat-induced toxicity and to elucidate the mechanisms underlying this protection. Our results showed that a pre-treatment with the BM extract, from 20.0μg/ml, protected the rat dopaminergic PC12 cell line against paraquat/diquat-induced toxicity in various cell survival assays. We demonstrated that BM pre-treatment, from 5.0μg/ml, could prevent the generation of intracellular reactive oxygen species (ROS), decreased mitochondrial superoxide levels and depolarized the mitochondria. BM pre-treatment also increased tyrosine hydroxylase (TH) levels and antioxidant defense systems such as γ-glutamylcysteine synthetase (γ-GCS) and thioredoxin1 (Trx1) levels. Furthermore, BM pre-treatment prevented the activation of Akt and heat shock protein90 (HSP90) proteins. Thus, our findings demonstrated that BM can protect PC12 cells through modulating cellular redox pathways which are altered in PD and could have a therapeutic application in the prevention of PD.
authors: INRS - Institut Armand Frappier, Quebec, Canada H7V 1B7.
authors: Manjeet
authors: M
authors: Singh
authors: Ven
authors: V
authors: Murthy
authors: Charles
authors: C
authors: Ramassamy
mesh_terms: D034681:Bacopa / Q000737:chemistry*; D004178:Diquat / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010269:Paraquat / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D006540:Herbicides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D004178:Diquat; D010269:Paraquat