Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera

Life Sci. 2003 Aug 8;73(12):1517-26. doi: 10.1016/s0024-3205(03)00476-4.

Abstract

There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Bacopa / chemistry*
  • Cells, Cultured
  • Comet Assay
  • Cytoprotection / drug effects
  • DNA / drug effects*
  • DNA Damage / drug effects*
  • DNA Fragmentation / drug effects
  • L-Lactate Dehydrogenase
  • Medicine, Ayurvedic*
  • Nitric Oxide Donors / toxicity*
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • S-Nitroso-N-Acetylpenicillamine / toxicity*

Substances

  • Nitric Oxide Donors
  • Plant Extracts
  • Reactive Oxygen Species
  • S-Nitroso-N-Acetylpenicillamine
  • DNA
  • L-Lactate Dehydrogenase