Department of Research, Development and Innovation, Nektium Pharma SL, 35118, Las Palmas de Gran Canaria, Spain.
Department of Research, Development and Innovation, Nektium Pharma SL, 35118, Las Palmas de Gran Canaria, Spain; Department of Botany and Plant Biotechnology, University of Johannesburg, Auckland Park, 2006, Johannesburg, South Africa.
J Ethnopharmacol. 2020 Oct 5;260:112996. doi: 10.1016/j.jep.2020.112996. Epub 2020 May 27.
Leaves of Mangifera indica L. have folk-uses in tropical regions of the world as health teas, as a remedy for exhaustion and fatigue, as a vegetable, and as a medicine. Mangifera indica leaf extract (MLE) had previously been demonstrated to alter brain electrical activity in-vivo. The aim of the present series of studies was to investigate whether mangiferin, a major compound in leaves and in MLE, is responsible for the neurocognitive activity of MLE, and if the CNS activities of MLE have translational potential.
MLE, tradename Zynamite, is produced by Nektium Pharma, Spain. Isolated mangiferin was tested in-vitro in radioligand binding and enzyme inhibition studies against 106 CNS targets. Changes in the electroencephalograms (EEG's) of MLE and mangiferin were recorded in-vivo from four brain regions. Two double blind randomized placebo-controlled crossover clinical trials were conducted, each with 16 subjects. At 90 min and at 60 min respectively, after oral intake of 500 mg MLE, EEG recordings, psychometric tests, mood state, and tolerability were studied.
Isolated mangiferin is a selective inhibitor of catechol-O-methyltransferase (COMT) with an IC50 of 1.1 μM, with no activity on the CNS targets of caffeine. Both mangiferin and MLE induce similar changes in long-term potentiation (LTP) in the hippocampus in-vitro, and induce a similar pattern of EEG changes in-vivo. In both translational clinical trials MLE was well tolerated, with no cardiovascular side-effects. In both studies MLE caused significant spectral changes in brain electrical activity in cortical regions during cognitive challenges, different to the attenuated spectral changes induced by caffeine. There were no significant changes in the psychometric tests other than reaction time for all groups. In the second study there was a trend to faster reaction time within group for MLE (p = 0.066) and the percentage improvement in reaction time for MLE compared to placebo was significant (p = 0.049). In the first study MLE improved all scores for Profile of Mood States (POMS), with the score for "fatigue" significantly improved (p = 0.015); in the second study the POMS score for "dejection" was improved in the caffeine group, p = 0.05.
Mangiferin is a COMT inhibitor of moderate potency and is the major CNS-active compound in MLE. Both mangiferin and MLE increase hippocampal LTP in-vitro, and induce a similar pattern of changes in brain electrical activity in-vivo. While the translational clinical trials of MLE are limited by being single dose studies in a small number of subjects, they provide the first clinical evidence that the extract is well tolerated with no cardiovascular side-effects, can induce changes in brain electrical activity, may give a faster reaction time, and decrease fatigue. These CNS activities support the reported folk-uses use of mango leaf tea as a substitute for tea and as a traditional remedy for fatigue and exhaustion. Extract Mangifera indica L., Zynamite, has nootropic potential, and larger clinical studies are needed to realise this potential.
芒果（Mangifera indica L.）的叶子在世界热带地区被民间用作健康茶，可缓解疲劳和倦怠，也可作为蔬菜和药物。芒果叶提取物（MLE）先前已被证明可以改变体内的大脑电活动。本系列研究的目的是研究芒果中的主要化合物芒果苷是否是 MLE 神经认知活性的原因，以及 MLE 的中枢神经系统活性是否具有转化潜力。
MLE，商品名为 Zynamite，由西班牙的 Nektium Pharma 生产。分离的芒果苷在体外的放射性配体结合和酶抑制研究中针对 106 个中枢神经系统靶标进行了测试。在四个大脑区域中，体内记录了 MLE 和芒果苷对脑电图（EEG）的变化。进行了两项双盲随机安慰剂对照交叉临床试验，每项试验均有 16 名受试者。分别在口服 500mg MLE 后 90 分钟和 60 分钟，记录 EEG 记录、心理测试、情绪状态和耐受性。
分离的芒果苷是一种对映体选择性儿茶酚-O-甲基转移酶（COMT）抑制剂，IC50 为 1.1μM，对咖啡因的中枢神经系统靶标无活性。芒果苷和 MLE 均可在体外诱导类似的长时程增强（LTP）变化，并且在体内诱导类似的脑电图变化模式。在这两项转化临床试验中，MLE 均耐受良好，无心血管副作用。在这两项研究中，MLE 引起皮质区域脑电活动的频谱发生明显变化，与咖啡因引起的频谱变化不同。除了所有组的反应时间外，心理测试没有明显变化。在第二项研究中，MLE 组的反应时间有更快的趋势（p=0.066），与安慰剂相比，MLE 组的反应时间改善百分比具有显著意义（p=0.049）。在第一项研究中，MLE 改善了所有心境状态量表（POMS）的评分，“疲劳”的评分明显改善（p=0.015）；在第二项研究中，咖啡因组的 POMS 评分中“忧郁”得到改善，p=0.05。
芒果苷是一种中等效力的 COMT 抑制剂，是 MLE 中主要的中枢神经系统活性化合物。芒果苷和 MLE 均可在体外增加海马体 LTP，并在体内诱导类似的脑电图变化模式。虽然 MLE 的转化临床试验受到限制，因为它们是在少数受试者中进行的单次剂量研究，但它们首次提供了临床证据，表明提取物耐受性良好，无心血管副作用，可引起脑电活动变化，可能会更快的反应时间，并减轻疲劳。这些中枢神经系统活性支持芒果叶茶被民间用作茶的替代品和传统疲劳和倦怠的治疗方法的说法。Mangifera indica L.提取物 Zynamite 具有神经认知潜力，需要更大规模的临床研究来实现这一潜力。
