Analysis of Mechanism of Antidepressant Effect of <italic style="font-style: italic">Sophora flavescens</italic> Seed Extract

ZHU Tian; WANG Ru; BIAN Lihua; LI Wenjing; LI Jie; CHEN Liangmian; WANG Zhimin; GAO Huimin; GUO Jianyou

doi:10.13422/j.cnki.syfjx.20231447

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Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract

更新时间：2023-11-20

- Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 24, Pages: 122-129(2023)
- 作者机构：
  
  1.中国科学院心理研究所，北京 100101
  2.中国科学院大学，北京 100049
  3.北京卫生职业学院，北京 101101
  4.中国中医科学院中药研究所，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231447
  CLC： R22;R28;R96;B84
- Published：20 December 2023，
  
  Published Online：15 September 2023，
  
  Received：07 July 2023，
- 稿件说明：
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朱天,王茹,边丽华等.苦参子提取物的抗抑郁作用机制分析[J].中国实验方剂学杂志,2023,29(24):122-129.

ZHU Tian,WANG Ru,BIAN Lihua,et al.Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(24):122-129.
朱天,王茹,边丽华等.苦参子提取物的抗抑郁作用机制分析[J].中国实验方剂学杂志,2023,29(24):122-129. DOI： 10.13422/j.cnki.syfjx.20231447.

ZHU Tian,WANG Ru,BIAN Lihua,et al.Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(24):122-129. DOI： 10.13422/j.cnki.syfjx.20231447.

摘要

目的

探讨苦参子提取物的抗抑郁作用及其分子作用机制。

方法

采用腹腔注射脂多糖（LPS）建立小鼠抑郁模型，设置正常组、模型组、氟西汀组（2.5 mg·kg

-1

），以及苦参子低、中、高剂量组（200、400、800 mg·kg

-1

），连续灌胃7 d，利用旷场实验、高架十字迷宫实验和强迫游泳实验考察苦参子提取物的抗抑郁作用。苏木素-伊红（HE）染色观察小鼠海马组织病理形态变化，蛋白免疫印迹法（Western blot）检测小鼠脑组织中G

/S特异性周期蛋白D

（Cyclin D

）、Wnt1蛋白、

-连环蛋白（

-catenin）、磷酸化糖原合成酶激酶-3

（p-GSK-3

）的蛋白表达水平。通过原位末端标记法（TUNEL）检测海马细胞凋亡情况。

结果

小鼠行为学结果显示，与正常组比较，模型组的旷场运动速度、旷场中间区运动距离、高架十字迷宫开臂停留时间均显著降低（

0.01），强迫游泳实验不动时间明显增加（

0.05）。与模型组比较，苦参子中、高剂量组的旷场运动速度、开臂停留时间增加（

0.05，

0.01），强迫游泳实验不动时间降低（

0.05）；苦参子高剂量组小鼠旷场中间区运动距离增加（

0.05）。HE染色结果发现与正常组比较，模型组小鼠海马神经元结构损伤。与模型组比较，给予苦参子低、中、高剂量组干预后，小鼠海马神经元结构病理状态减轻，神经元增多、排列整齐、胞浆清楚。Western blot结果显示，小鼠注射LPS后脑组织中Wnt1及

-catenin蛋白表达水平显著降低（

0.01），Cyclin D

及p-GSK-3

蛋白表达水平显著增加（

0.01）；与模型组比较，苦参子中、高剂量组小鼠脑组织中Wnt1和

-catenin蛋白表达水平均显著增加（

0.01），而Cyclin D

和p-GSK-3

蛋白表达量则显著降低（

0.01）。TUNEL染色结果显示，模型组小鼠的海马细胞凋亡率较正常组显著增加（

0.01），与模型组比较，苦参子中、高剂量组小鼠海马细胞凋亡率显著降低（

0.01）。

结论

苦参子提取物可有效改善LPS所致抑郁小鼠的抑郁严重程度，其分子机制与调控Wnt/

-catenin信号转导通路介导的神经炎症和海马神经元凋亡有关。

Abstract

Objective

To explore the antidepressant effect of

Sophora flavescens

seed extract and its molecular mechanism.

Method

A mouse depression model was established by intraperitoneal injection of lipopolysaccharide（LPS）， and normal group， model group， fluoxetine group（2.5 mg·kg

-1

）， and

S. flavescens

seed low， medium and high dose groups（200， 400， 800 mg·kg

-1

） were set up for 7 d of consecutive gavage. Then the antidepressant effect of

S. flavescens

seed extract was evaluated by using open field test， elevated plus maze test and forced swimming test. Pathological morphological changes in the hippocampal tissue was observed by hematoxylin-eosin（HE） staining. Protein expression levels of G

/S-specific cyclin D

（Cyclin D

）， Wnt1，

-catenin and phosphorylated glycogen synthase kinase-3

（p-GSK-3

） in mouse brain tissues were detected by Western blot. Hippocampal cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL）.

Result

The results of mouse behavioral experiments showed that compared with the normal group， the speed of movement in the open field and the distance of movement in the central area of the open field， and the time spent on the open arms of the elevated plus maze were significantly reduced in the model group（

0.01）， while immobility time in the forced swimming test was significantly increased（

0.05）. Compared with the model group， the

S. flavescens

seed medium and high dose groups had increased speed of movement in the open field test and time spent on the open arms of the elevated plus maze test（

0.05，

0.01）， and decreased immobility time in the forced swimming test（

0.05）， the distance of movement in the central area of the open field test increased in the high dose group（

0.05）. HE staining results showed that compared with the normal group， the hippocampal neuron structure of mice in the model group was damaged. Compared with the model group， after treatment of

S. flavescens

seed extract， the pathological state of the mouse hippocampal neuron structure was alleviated， and the neurons increased， were neatly arranged， and the cytoplasm was clear. Western blot results showed that the protein expression levels of Wnt1 and

-catenin in mouse brain tissue were significantly decreased（

0.01）， while the protein expression levels of Cyclin D

and p-GSK-3

were significantly increased（

0.01） after LPS injection. Compared with the model group， protein expression levels of Wnt1 and

-catenin in brain tissue of

S. flavescens

seed medium and high dose groups were significantly increased（

0.01）， while the protein expression levels of Cyclin D

and p-GSK-3

were significantly decreased（

0.01）. TUNEL staining results showed that the hippocampal cell apoptosis rate in the model group was significantly increased compared with that of the normal group（

0.01）， while the hippocampal cell apoptosis rate in the

S. flavescens

seed medium and high dose groups was significantly decreased compared with that of the model group（

0.01）.

Conclusion

S. flavescens

seed extract can effectively improve the severity of depression in LPS-induced depressed mice， and its molecular mechanism is related to the regulation of neuroinflammation and hippocampal neuronal apoptosis mediated by Wnt/

-catenin signaling pathway.

关键词

苦参子提取物氧化苦参碱二肽脂多糖（LPS）抗抑郁作用Wnt/β-连环蛋白信号通路作用机制

Keywords

Sophora flavescens seed extractoxymatrinedipeptidelipopolysaccharide（LPS）antidepressant effectWnt/β-catenin signaling pathwaymechanism of action

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Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract

DOI：10.13422/j.cnki.syfjx.20231447

摘要

Abstract

关键词

Keywords

references