Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice

Despite the increasing popularity of Centella asiatica (a well known plant in ayurvedic medicine) globally,
evidence demonstrating its protective efficacy against neurotoxicants in animal models is limited. 3-
Nitropropionic acid (3-NPA), a fungal toxin is a well known neurotoxicant which induces selective striatal
pathology similar to that seen in Huntington’s disease. The present study aimed to understand the
neuroprotective efficacy of a standardized aqueous extract of C. asiatica (CA) against 3-NPA-induced early
oxidative stress and mitochondrial dysfunctions in striatum and other brain regions. We determined the
extent of oxidative stress in cytosol and mitochondria of brain regions of male mice (4 wk old) given CA
prophylaxis (5 mg/kg bw) for 10 days followed by 3-NPA administration (i.p., 75 mg/kg bw/d) on the last
2 days. The neurotoxicant elicited marked oxidative stress in the untreatedmice as evidenced by elevated
levels of malondialdehyde, ROS levels and hydroperoxides in the striatum (cytosol and mitochondria),
while CA prophylaxis completely attenuated the 3-NPA-induced oxidative stress. 3-NPA also caused
significant oxidative stress and protein oxidation in cytosol/mitochondria of other brain regions as well
which were predominantly abolished by CA prophylaxis. Significant depletion of GSH levels, total thiols
and perturbations in antioxidant enzymic defences in striatum and other brain regions discernible
among 3-NPA administered mice were also protected with CA prophylaxis. Interestingly, CA prophylaxis
offered varying degree of protection against 3-NPA-induced mitochondrial dysfunctions viz., reduction in
the activity of succinic dehydrogenase, ETC enzymes and decreased mitochondrial viability. Collectively
these findings clearly suggest that short-term oral intake of a standardized aqueous extract of CA confers
marked resistance against the 3-NPA-induced oxidative stress and mitochondrial dysfunctions in brain.
Although the precisemechanism/s underlying the prophylactic efficacy of CA merit further investigation,
based on these findings, it is hypothesized that it may be wholly or in part related to the enhancement of
GSH, thiols and antioxidant machinery in the brain regions of prepubertal mice.