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

Abstract

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 untreated mice 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 precise mechanism/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.