Shinomol George K
Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CFTRI, a CSIR Laboratory), Mysore 570020, India.
Neurotoxicology. 2008 Nov;29(6):948-57. doi: 10.1016/j.neuro.2008.09.009. Epub 2008 Sep 27.
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 (4wk old) given CA prophylaxis (5mg/kgbw) for 10 days followed by 3-NPA administration (i.p., 75mg/kgbw/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.
尽管积雪草（阿育吠陀医学中一种著名的植物）在全球越来越受欢迎，但在动物模型中证明其对神经毒素具有保护作用的证据有限。3-硝基丙酸（3-NPA）是一种真菌毒素，是一种众所周知的神经毒素，可诱导与亨廷顿舞蹈病相似的选择性纹状体病变。本研究旨在了解积雪草标准化水提取物（CA）对3-NPA诱导的纹状体和其他脑区早期氧化应激和线粒体功能障碍的神经保护作用。我们测定了雄性小鼠（4周龄）脑区细胞质和线粒体中的氧化应激程度，这些小鼠在接受10天的CA预防（5mg/kg体重）后，在最后2天腹腔注射3-NPA（75mg/kg体重/天）。神经毒素在未治疗的小鼠中引发了明显的氧化应激，纹状体（细胞质和线粒体）中丙二醛、活性氧水平和氢过氧化物水平升高证明了这一点，而CA预防完全减轻了3-NPA诱导的氧化应激。3-NPA还在其他脑区的细胞质/线粒体中引起了显著的氧化应激和蛋白质氧化，而CA预防主要消除了这些氧化应激。在给予3-NPA的小鼠中，纹状体和其他脑区中谷胱甘肽水平、总硫醇的显著消耗以及抗氧化酶防御的紊乱也通过CA预防得到了保护。有趣的是，CA预防对3-NPA诱导的线粒体功能障碍提供了不同程度的保护，即琥珀酸脱氢酶、电子传递链酶的活性降低以及线粒体活力下降。总的来说，这些发现清楚地表明，短期口服CA标准化水提取物可显著抵抗3-NPA诱导的脑内氧化应激和线粒体功能障碍。尽管CA预防作用的确切机制值得进一步研究，但基于这些发现，推测其可能全部或部分与青春期前小鼠脑区中谷胱甘肽、硫醇和抗氧化机制的增强有关。
