Department of Pharmacognosy, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Biomed Pharmacother. 2023 Nov;167:115382. doi: 10.1016/j.biopha.2023.115382. Epub 2023 Sep 29.
Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer's disease (AD). Meanwhile, β-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.
朱顶红（Lindl）是石蒜科的一种植物，以其具有广泛生物活性的化学多样性生物碱而闻名。许多报道表明，氧化应激在阿尔茨海默病（AD）的早期阶段起直接作用。同时，β-淀粉样前体蛋白裂解酶 1（BACE-1）是治疗 AD 的分子靶标。我们旨在研究朱顶红花、鳞茎和地上部分的化学成分、抗氧化、BACE-1 和 AChE 酶抑制活性。结果表明，与鳞茎和地上部分相比，总根具有最强的自由基清除活性。与鳞茎和地上部分相比，乙醇根提取物对 BACE-1 具有最强的抑制活性（IC = 0.02±0.001μg/mL）。此外，总根提取物比总鳞茎和地上部分更能减轻 AChE 酶的活性，IC 值分别为（0.06±0.02、0.58±0.3 和 1.89±0.42μg/mL）。基于生物测定的酸碱分步萃取证实，根部分特别是二氯甲烷和乙酸乙酯部分对 BACE-1 具有更强的抑制活性，IC 值分别为（0.21±0.60 和 0.01±0.001μg/mL）。通过 UPLC-MS 对朱顶红花根的乙酸乙酯和二氯甲烷部分进行分析，分别鉴定出八种酚类和十三种生物碱。对 BACE-1 蛋白的分子对接研究表明，石蒜科碱二己糖苷、朱顶红胺和朱顶红灵是最有前途的候选物。需要进一步研究上述小分子的抗 AD 潜力。
