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-NPA-induced 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.