Effect of Aloe-emodin on A<italic style="font-style: italic">β</italic><sub>42</sub> Aggregation and Cytotoxicity in Presence of Al<sup>3+</sup>

Ni YAO; Chuyin WANG; Xitong ZHAO; Yang CHEN; Qian ZHANG; Fang FANG; Jun GUAN

doi:10.13422/j.cnki.syfjx.20212153

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Effect of Aloe-emodin on Aβ₄₂ Aggregation and Cytotoxicity in Presence of Al³⁺

更新时间：2022-08-11

- Effect of Aloe-emodin on Aβ₄₂ Aggregation and Cytotoxicity in Presence of Al³⁺
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 18, Pages: 99-107(2022)
- 作者机构：
  
  北京中医药大学中药学院，北京 102488
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20212153
  CLC： R22;R28;R96;O657.34
- Published：20 September 2022，
  
  Published Online：17 November 2021，
  
  Received：30 September 2021，
- 稿件说明：
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姚妮,王楚茵,赵希彤等.芦荟大黄素对Al³⁺存在下Aβ₄₂聚集和细胞增殖抑制作用的影响[J].中国实验方剂学杂志,2022,28(18):99-107.

YAO Ni,WANG Chuyin,ZHAO Xitong,et al.Effect of Aloe-emodin on Aβ₄₂ Aggregation and Cytotoxicity in Presence of Al³⁺[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):99-107.
姚妮,王楚茵,赵希彤等.芦荟大黄素对Al³⁺存在下Aβ₄₂聚集和细胞增殖抑制作用的影响[J].中国实验方剂学杂志,2022,28(18):99-107. DOI： 10.13422/j.cnki.syfjx.20212153.

YAO Ni,WANG Chuyin,ZHAO Xitong,et al.Effect of Aloe-emodin on Aβ₄₂ Aggregation and Cytotoxicity in Presence of Al³⁺[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):99-107. DOI： 10.13422/j.cnki.syfjx.20212153.

摘要

目的

在体外研究芦荟大黄素（AE）对金属铝离子（Al

）诱导的

-淀粉样蛋白42（A

）聚集的抑制作用，以及对已形成的A

-Al

聚集体的解聚作用，并考察其对Al

存在下A

聚集产生的细胞增殖抑制作用的影响。

方法

设置A

组、A

+Al

组、A

+AE组、A

+Al

+AE组，以及解聚作用考察实验，应用硫黄素T（ThT）荧光试验、透射电子显微镜（TEM）、动态光散射法（DLS）及噻唑蓝（MTT）细胞增殖抑制作用试验分别检测各组A

的聚集纤维化过程、聚集体形貌、聚集体尺寸及细胞增殖抑制作用。

结果

与A

组比较，Al

可促进A

聚集，使ThT荧光强度升高至124.48%，诱导A

聚集形成粒径较大的纤维束，并显著降低人神经母细胞瘤细胞SH-SY5Y的细胞活力（

0.01），使细胞生存率降低至51.05%。AE不仅能抑制A

聚集，而且可浓度依赖性地抑制Al

诱导的A

聚集；与A

+Al

组比较，高浓度AE使ThT荧光强度降低至41.66%，改变多肽聚集途径形成粒径较小的无定型结构聚集体，并显著抑制Al

诱导A

产生的细胞增殖抑制作用（

0.01），使细胞生存率恢复至84.87%。解聚研究发现，AE可解聚A

-Al

聚集体，使已形成的聚集体消失，形成一些毒性较低的小粒径短纤维及无定型结构聚集体。

结论

AE可抑制Al

存在下的A

聚集及细胞增殖抑制作用，解聚已形成的A

-Al

聚集体，缓解其产生的细胞增殖抑制作用，为探索AE治疗阿尔茨海默病的作用机制奠定基础。

Abstract

Objective

To study the inhibitory effect of aloe-emodin （AE） on aluminum ion （Al

）-induced

-amyloid protein 42 （A

）

aggregation and its depolymerization on formed A

-Al

aggregates

in vitro

， and to investigate the effect of AE on the cytotoxicity of A

aggregation in the presence of Al

Method

The A

group， A

+Al

group， A

+AE group， A

+Al

+AE group and the depolymerization test group were set up in the experiment. The aggregation fibrosis process， aggregation morphology， aggregation size and cytotoxicity of A

in each group were detected by thioflavin T （ThT） fluorescence assay， transmission electron microscopy （TEM）， dynamic light scattering （DLS） experiment and thiazolyl blue （MTT） cytotoxicity assay.

Result

Compared with the A

group， Al

could promote A

aggregation， increase the fluorescence intensity of ThT by 124.48%， induce the aggregation of A

to form fiber bundles with larger particle size， and significantly reduce the cell viability of human neuroblastoma SH-SY5Y cells （

0.01）， thus reducing the cell survival rate to 51.05%. AE not only inhibited A

aggregation， but also inhibited Al

-induced A

aggregation in a concentration-dependent manner. Compared with the A

+Al

group， high concentration of AE could reduce the ThT fluorescence intensity to 41.66%， and change the polypeptide aggregation pathway to form amorphous aggregates with small particle size. Besides， it significantly inhibited the cytotoxicity of A

induced by Al

（

0.01）， and restored the cell survival rate to 84.87%. Further depolymerization was conducted， AE could depolymerize A

-Al

aggregates to make the formed aggregates disappear and form some small-particle short fibers and amorphous structure aggregates with low toxicity.

Conclusion

AE can inhibit A

aggregation and cytotoxicity in the presence of Al

， depolymerize the formed A

-Al

aggregates and alleviate the cytotoxicity， thus laying the foundation for exploring the mechanism of AE in the treatment of Alzheimer's disease.

关键词

阿尔茨海默病β-淀粉样蛋白芦荟大黄素聚集抑制剂铝离子（Al3+）螯合作用细胞增殖抑制作用

Keywords

Alzheimer's diseaseβ-amyloid proteinaloe-emodinaggregation inhibitoraluminum ion （Al3+）chelationcytotoxicity

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⁰

Effect of Aloe-emodin on Aβ42 Aggregation and Cytotoxicity in Presence of Al3+

DOI：10.13422/j.cnki.syfjx.20212153

摘要

Abstract

关键词

Keywords

references

Effect of Aloe-emodin on Aβ₄₂ Aggregation and Cytotoxicity in Presence of Al³⁺