Neuromodulatory Propensity of Bacopa monnieri Leaf Extract Against 3-Nitropropionic Acid-Induced Oxidative Stress: In Vitro and In Vivo Evidences.

We previously reported the propensity of
Bacopa monnieri (BM) leaf powder to modulate endogenous
levels of oxidative stress markers in the brain of
prepubertal mice. In this study, we tested the hypothesis
that pretreatment with an alcoholic extract of BM (BME)
could provide neuroprotection against 3-nitropropionic
acid (3-NPA)-induced oxidative stress under in vitro and in
vivo conditions. In chemical systems, BME exhibited
multiple free radical scavenging ability. Further, BME
pretreatment completely abolished 3-NPA-induced oxidative
stress response in brain (striatum, St) mitochondria in
vitro. Likewise, pretreatment of dopaminergic (N27 cell
lines) cells with BME not only abrogated the generation of
reactive oxygen species (ROS) levels, but also offered
marked protection against 3-NPA-mediated cytotoxicity.
These findings were further validated employing a 3-NPA
mice model in vivo. We determined the degree of oxidative
stress induction, redox status, enzymic antioxidants, protein
oxidation, and cholinergic function in various brain
regions of male mice provided with BME for 10 days
(prophylaxis) followed by 3-NPA challenge (75 mg/kg bw/
day, i.p.). BME prophylaxis completely prevented 3-NPAinduced
oxidative dysfunctions in St and other brain
regions. 3-NPA-induced robust elevation of oxidative
markers (malondialdehyde levels, ROS generation,
hydroperoxide levels and protein carbonyls) in cytosol of
brain regions was predominantly abolished among mice
given BME prophylaxis. Interestingly, BME prophylaxis
also prevented the depletion of reduced glutathione, thiol
levels, and perturbations in antioxidant enzymes caused by
3-NPA. Collectively these findings provide evidence on the
significant prophylactic neuroprotective efficacy of BME
in prepubertal mice brain. Based on these data, it is
hypothesized that BME can serve as a useful adjuvant in
protecting brain against oxidative-mediated neurodegenerative
disorders involving oxidative stress conditions.