Grupo de Investigación en Sustancias Bioactivas, Facultad de Química Farmacéutica, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, Faculty of Medicine, University of Antioquia, Calle 70 No. 52-21, Medellín, Colombia.
Life Sci. 2015 Feb 1;122:42-50. doi: 10.1016/j.lfs.2014.12.011. Epub 2014 Dec 19.
Amaryllidaceae alkaloids exhibit a wide range of physiological effects, of which the acetylcholinesterase (AChE) inhibitory activity is the most relevant. However, scientific evidence related to their neuroprotective effectiveness against glutamate-induced toxicity has been lacking. Thus, the purpose of this study was to conduct a comparative study of the neuroprotective activity and the AChE inhibitory activity of species of Amaryllidaceae.
The neuroprotective activity against glutamate-induced toxicity was measured in rat cortical neurons and the Ellman method was employed for the quantification of acetylcholinesterase inhibitory activity of alkaloidal extracts of five species of Amaryllidaceae (Crinum jagus, Crinum bulbispermum, Hippeastrum barbatum, Hippeastrum puniceum and Zephyranthes carinata). The alkaloid Amaryllidaceae patterns based on GC/MS analyses were also investigated.
The results showed that the alkaloidal extract from C. jagus presented a high neuroprotective activity in both pre- and post-treatments against a glutamate excitotoxic stimulus. Furthermore, the alkaloid extracts from C. jagus and Z. carinata revealed an inhibitory activity of AChE from the electric eel with IC50 values of 18.28±0.29 and 17.96±1.22μg/mL, respectively. In addition, 46 alkaloids were detected by GC/MS, and 20 of them were identified based on their mass spectra and retention index. The results suggest that the neuroprotective effects might be associated with lycorine and crinine-type alkaloids, whereas the acetylcholinesterase enzyme inhibitory activity could be related to galanthamine and lycorine-type alkaloids, although not based on synergistic processes.
In summary, Amaryllidaceae species are sources of alkaloids with potential use for Alzheimer's disease.
石蒜科生物碱具有广泛的生理作用，其中乙酰胆碱酯酶（AChE）抑制活性最为相关。然而，缺乏关于其对抗谷氨酸诱导的毒性的神经保护效力的科学证据。因此，本研究的目的是对石蒜科几种植物的神经保护活性和 AChE 抑制活性进行比较研究。
采用大鼠皮质神经元测定法测定抗谷氨酸诱导毒性的神经保护活性，并采用 Ellman 法测定 5 种石蒜科植物（Crinum jagus、Crinum bulbispermum、Hippeastrum barbatum、Hippeastrum puniceum 和 Zephyranthes carinata）生物碱提取物的乙酰胆碱酯酶抑制活性。还研究了基于 GC/MS 分析的石蒜科生物碱图谱。
结果表明，C. jagus 的生物碱提取物在谷氨酸兴奋毒性刺激的预处理和后处理中均表现出较高的神经保护活性。此外，C. jagus 和 Z. carinata 的生物碱提取物对电鳗 AChE 表现出抑制活性，IC50 值分别为 18.28±0.29 和 17.96±1.22μg/mL。此外，通过 GC/MS 检测到 46 种生物碱，其中 20 种根据其质谱和保留指数进行了鉴定。结果表明，神经保护作用可能与石蒜碱和石蒜属生物碱有关，而乙酰胆碱酯酶抑制活性可能与加兰他敏和石蒜属生物碱有关，尽管不是基于协同作用过程。
总之，石蒜科植物是具有治疗阿尔茨海默病潜力的生物碱的来源。
