Study on the promotion effect mechanism of ethanol extract from <italic style="font-style: italic">Atractylodes macrocephala </italic>on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway

CHU Shuang; WU Yanrao; WU Limin; CUI Zhenghao; WANG Pan; SUN Yiran; XIE Zhishen; ZHANG Zhenqiang

doi:10.6039/j.issn.1001-0408.2023.01.03

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Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway

更新时间：2023-02-22

- Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway
- ZHONGGUO YAOFANG Vol. 34, Issue 1, Pages: 12-17(2023)
- 作者机构：
  
  1.河南中医药大学中医药科学院，郑州　450046
  2.河南中医药大学第一附属医院药学部，郑州　450052
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.01.03
  CLC： R965
- Published：15 January 2023，
  
  Received：06 July 2022，
  
  Revised：16 November 2022，
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初双,吴延娆,吴丽敏等.白术乙醇提取物调节PPAR-γ信号通路促进小胶质细胞摄取及降解Aβ的作用机制研究 ^Δ[J].中国药房,2023,34(01):12-17.

CHU Shuang,WU Yanrao,WU Limin,et al.Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway[J].ZHONGGUO YAOFANG,2023,34(01):12-17.
初双,吴延娆,吴丽敏等.白术乙醇提取物调节PPAR-γ信号通路促进小胶质细胞摄取及降解Aβ的作用机制研究 ^Δ[J].中国药房,2023,34(01):12-17. DOI： 10.6039/j.issn.1001-0408.2023.01.03.

CHU Shuang,WU Yanrao,WU Limin,et al.Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway[J].ZHONGGUO YAOFANG,2023,34(01):12-17. DOI： 10.6039/j.issn.1001-0408.2023.01.03.

摘要

目的

基于过氧化物酶体增殖物激活受体γ（PPAR-γ）信号通路研究白术乙醇提取物（EEAM）促进小胶质细胞摄取及降解β淀粉样蛋白（Aβ）的作用机制。

方法

以小鼠神经小胶质细胞BV2为研究对象，采用激光共聚焦荧光显微镜观察EEAM（低、中、高剂量分别为0.3、0.4、0.5 mg/mL，下同）对细胞摄取和降解Aβ的影响；利用人胚胎肾细胞HEK293考察EEAM对PPAR-γ萤光素酶转录活性的影响；采用免疫荧光法考察EEAM对PPAR-γ核移位的影响；以Aβ

1-42

诱导阿尔茨海默病BV2细胞模型，并采用定量聚合酶链式反应法考察EEAM对PPAR-γ下游靶基因（

Lxra

、

Lxrb

、

Abca1

、

Abcg1

、

Cd36

、

Sra

和

Apoe

）mRNA表达的影响。

结果

Aβ摄取实验结果显示，经中、高剂量EEAM干预后，BV2细胞中Aβ荧光强度均显著升高（

＜0.05）；Aβ降解实验结果显示，经中、高剂量EEAM干预后，BV2细胞中Aβ荧光强度均显著降低（

＜0.05）。经各剂量EEAM干预后，HEK293细胞中PPAR-γ萤光素酶转录活性均显著升高

（P

＜0.05），BV2细胞中和细胞核中PPAR-γ蛋白的荧光强度（低剂量组除外）均显著升高（

＜0.05），BV2细胞中

Lxra

、

Lxrb

、

Abca1

、

Abcg1

、

Cd36

、

Sra

、

Apoe

mRNA的表达水平均显著升高（

＜0.05）。

结论

EEAM可通过激活PPAR-γ信号通路，促进小胶质细胞对Aβ的摄取与降解作用，进而改善阿尔茨海默病。

Abstract

OBJECTIVE

To explore the effect mechanism of ethanol extract from

Atractylodes macrocephala

（EEAM） on microglial phagocytosis and degradation of amyloid β （Aβ） based on peroxisome proliferator-activated receptor γ （PPAR-γ） signaling pathway.

METHODS

Taking neuromicroglial cell BV2 as subjects， confocal microscopy was used to observe the effects of EEAM （0.3， 0.4， 0.5 mg/mL， similarly hereinafter） on phagocytosis and degradation of Aβ in microglia. Human embryonic kidney cell HEK293 was used to investigate the effects of EEAM on luciferase transcriptional activity of PPAR-γ. The effect of EEAM on nuclear translocation of PPAR-γ was investigated by immunofluorescence. Alzheimer’s disease BV2 cell model was induced by Aβ

1-42

， and quantitative polymerase chain reaction was used to investigate the effects of EEAM on mRNA expressions of PPAR-γ downstream target genes （

Lxra

，

Lxrb

，

Abca1

，

Abcg1

，

Cd36

，

Sra

and

Apoe

）.

RESULTS

The results of Aβ uptake experiment showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells increased significantly （

＜0.05）. The degradation experiment of Aβ showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells decreased significantly （

＜0.05）. After the intervention of different doses of EEAM， luciferase transcriptional activity of PPAR-γ in HEK293 cells increased significantly （

＜0.05）； fluorescence intensity of PPAR-γ in BV2 cells and nuclei （except for low-dose group） increased significantly （

＜0.05）. mRNA expressions of

Lxra

，

Lxrb

，

Abca1

，

Abcg1

，

Cd36

，

Sra

and

Apoe

in BV2 cells were increased significantly （

＜0.05）.

CONCLUSIONS

EEAM can promote the uptake and degradation of Aβ in microglia by activating PPAR-γ signaling pathway， thus improving Alzheimer’s disease.

关键词

白术乙醇提取物过氧化物酶体增殖物激活受体γ小胶质细胞β淀粉样蛋白阿尔茨海默病

Keywords

PPAR-γmicrogliaamyloid βAlzheimer’s disease

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Study on the promotion effect mechanism of ethanol extract from Atractylodes macrocephala on microglia phagocytosis and degradation of Aβ based on regulating PPAR-γ signaling pathway

DOI：10.6039/j.issn.1001-0408.2023.01.03

摘要

Abstract

关键词

Keywords

references