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从柚子籽中分离出的柠檬苦素通过调节细胞凋亡,经由PI3K/AKT信号通路拮抗Aβ25-35介导的神经元损伤。

Limonin Isolated From Pomelo Seed Antagonizes Aβ25-35-Mediated Neuron Injury via PI3K/AKT Signaling Pathway by Regulating Cell Apoptosis.

作者信息

Qiu Yuanxin, Yang Jingxian, Ma Lukai, Song Mingyue, Liu Guo

机构信息

School of Food Science and Engineering, Zhongkai University of Agricultural Engineering, Guangzhou, China.

Guangdong Provincial Key Laboratory of Lingnan Specialty Food Science and Technology, Guangzhou, China.

出版信息

Front Nutr. 2022 May 12;9:879028. doi: 10.3389/fnut.2022.879028. eCollection 2022.

DOI:10.3389/fnut.2022.879028
PMID:35634407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9133815/
Abstract

Pomelo seed as a by-product from pomelo consumption is rich in bioactive compounds, however, a huge volume of pomelo seed was disposed as wastes, the comprehensive utilization of pomelo seed could not only generate valued-added products/ingredients, but also decrease the environmental pollution. In this study, the main active substance limonin in pomelo seed was considered as a high-value bioactive compound. The purification of limonin from pomelo seed was investigated, and the neuroprotective and mechanism were characterized. The UPLC-MS/MS results indicated that 29 compounds in pomelo seed were identified, including 14 flavonoids, 3 limonids, 9 phenols and 3 coumarins. Moreover, high purity of limonin was obtained by crystallization and preparative-HPLC. Furthermore, limonin pretreatment can antagonize the cell damage mediated by Aβ in a concentration-dependent relationship. The regulation of Bax/Bcl-2, expression of caspase-3 protein and the activation of PI3K/Akt signaling pathway were observed in the cells pretreated with limonin. Treatment of PC12 cells with PI3K inhibitor LY294002 weakened the protective effect of limonin. These results indicated that limonin prevented Aβ-induced neurotoxicity by activating PI3K/Akt, and further inhibiting caspase-3 and up-regulating Bcl-2. This study enables comprehensive utilization of pomelo seed as by-product and offers a theoretical principle for a waste-to-wealth solution, such as potential health benefits of food ingredient and drug.

摘要

柚子籽作为柚子消费的副产品,富含生物活性化合物。然而,大量的柚子籽被作为废物处理,柚子籽的综合利用不仅可以生产高附加值的产品/成分,还可以减少环境污染。在本研究中,柚子籽中的主要活性物质柠檬苦素被视为一种高价值的生物活性化合物。研究了从柚子籽中纯化柠檬苦素的方法,并对其神经保护作用及机制进行了表征。超高效液相色谱-串联质谱(UPLC-MS/MS)结果表明,柚子籽中鉴定出29种化合物,包括14种黄酮类化合物、3种柠檬苦素类化合物、9种酚类化合物和3种香豆素类化合物。此外,通过结晶和制备型高效液相色谱法获得了高纯度的柠檬苦素。此外,柠檬苦素预处理可以浓度依赖性地拮抗Aβ介导的细胞损伤。在用柠檬苦素预处理的细胞中观察到Bax/Bcl-2的调节、caspase-3蛋白的表达以及PI3K/Akt信号通路的激活。用PI3K抑制剂LY294002处理PC12细胞减弱了柠檬苦素的保护作用。这些结果表明,柠檬苦素通过激活PI3K/Akt,进一步抑制caspase-3并上调Bcl-2来预防Aβ诱导的神经毒性。本研究实现了对柚子籽副产品的综合利用,并为变废为宝提供了理论依据,如食品成分和药物潜在的健康益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/300e7497f843/fnut-09-879028-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/b71be880a93c/fnut-09-879028-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/fee9dca45be2/fnut-09-879028-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/598cab224de3/fnut-09-879028-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/d24a304bef06/fnut-09-879028-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/300e7497f843/fnut-09-879028-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/b71be880a93c/fnut-09-879028-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/fee9dca45be2/fnut-09-879028-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/598cab224de3/fnut-09-879028-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/d24a304bef06/fnut-09-879028-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d85/9133815/300e7497f843/fnut-09-879028-g0005.jpg

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