Kaur Mandeep, Prakash Atish, Kalia Ajudhia Nath
Nutr Neurosci. 2016;19(2):70-8. doi: 10.1179/1476830515Y.0000000022. Epub 2015 Apr 21.
To isolate the neuroprotective component from Convolvulus pluricaulis Chois. (Convolvulaceae) which can be used as a lead molecule in the treatment of Huntington's disease (HD).
The methanolic extract of whole plant was fractionated into four fractions; chloroform, ethyl acetate, n-butanol, and aqueous fraction. The chloroform and ethyl acetate fractions were pooled on the basis of antioxidant activity and TLC profile and charged into silica gel column. Four subfractions were collected from column (FrA, FrB, FrC, and FrD) and further assessed for antioxidant potential by 2,2-diphenyl-1-picrylhydrazyl in vitro assay. 3-Nitropropionic acid (3-NP) was administered to Wister rats for induction of HD. Different fractions were administered for 14 days. Different behavioral alterations were assessed in between study period. Animals were euthanized immediately following the last behavioral session, and biochemical parameters were measured.
Systemic administration of 3-NP showed marked motor deficits and oxidative damage in rats. Only FrB showed significant antioxidant activity and on further purification gave pure compound (scopoletin). Our study showed that FrB (20 mg/kg) pre-treatment significantly attenuated the loss in body weight, improved the locomotor activity, grip strength, and gait abnormalities. It also has attenuated the increased malondialdehyde and nitrite levels, and restored superoxide dismutase and reduced GSH enzyme activity in the striatum and cortex in 3-NP-treated groups. These results suggest that C. pluricaulis Chois. exhibits a neuroprotective effect by accelerating brain antioxidant defense mechanisms in 3-NP-treated rats.
从旋花科植物打碗花中分离出具有神经保护作用的成分,该成分可作为治疗亨廷顿舞蹈病(HD)的先导分子。
将全株植物的甲醇提取物分成四个部分;氯仿、乙酸乙酯、正丁醇和水相部分。根据抗氧化活性和薄层色谱图谱将氯仿和乙酸乙酯部分合并,装入硅胶柱。从柱上收集四个亚部分(FrA、FrB、FrC和FrD),并通过2,2-二苯基-1-苦基肼体外试验进一步评估其抗氧化潜力。给Wistar大鼠注射3-硝基丙酸(3-NP)以诱导HD。给予不同部分药物14天。在研究期间评估不同的行为改变。在最后一次行为测试后立即对动物实施安乐死,并测量生化参数。
全身注射3-NP可使大鼠出现明显的运动功能障碍和氧化损伤。只有FrB显示出显著的抗氧化活性,进一步纯化后得到纯化合物(东莨菪素)。我们的研究表明,FrB(20mg/kg)预处理可显著减轻体重减轻,改善运动活性、握力和步态异常。它还减轻了3-NP处理组纹状体和皮质中丙二醛和亚硝酸盐水平的升高,并恢复了超氧化物歧化酶活性,降低了谷胱甘肽酶活性。这些结果表明,打碗花通过加速3-NP处理大鼠的脑抗氧化防御机制而发挥神经保护作用。