Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice

Context Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as “Huangteng.” The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported.Objectives This study inve...

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Main Authors: Zhongmei He, He Yu, Hong Wu, Lili Su, Kun Shi, Yan Zhao, Ying Zong, Weijia Chen, Rui Du
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Pharmaceutical Biology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/13880209.2022.2099429
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author Zhongmei He
He Yu
Hong Wu
Lili Su
Kun Shi
Yan Zhao
Ying Zong
Weijia Chen
Rui Du
author_facet Zhongmei He
He Yu
Hong Wu
Lili Su
Kun Shi
Yan Zhao
Ying Zong
Weijia Chen
Rui Du
author_sort Zhongmei He
collection DOAJ
description Context Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as “Huangteng.” The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported.Objectives This study investigates the antidepressant effects of AFR by network pharmacology and verification experiments.Materials and methods Compound-Target-Pathway (C-P-T) network of FR and depression was constructed through network pharmacology. In vitro, HT-22 cells were treated with corticosterone (CORT) solution (0.35 mg/mL), then AFR (0.05 mg/mL) solution and inhibitor AZD6244 (14 μM/mL) or BAY11-7082 (10 μM/mL) were added, respectively. The cell viability was detected by CCK-8. In vivo, C57BL/6 mice were divided into 5 groups, namely the normal group, the CUMS group, the AFR (400 mg/kg) group, and the 2 groups that were simultaneously administered the inhibitory group AZD6244 (8 mg/kg) and BAY11-7082 (5 mg/kg). Western blotting was used to assess the expression level of the proteins.Results AFR could protect HT-22 cells from CORT-induced damage and increase the cell viability from 49.12 ± 3.4% to 87.26 ± 1.5%. Moreover, AFR significantly increased the levels of BDNF (1.3, 1.4-fold), p-ERK (1.4, 1.2-fold) and p-CERB (1.6, 1.3-fold), and decreased the levels of NLRP3 (11.3%, 31.6%), ASC (19.2%, 34.2%) and caspase-1 (18.0%, 27.6%) in HT-22 cells and the hippocampus, respectively.Discussion and conclusions AFR can improve depressive-like behaviours and can develop drugs for depression treatment. Further studies are needed to validate its potential in clinical medicine.
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spelling doaj.art-87b4ac129d824d02b363f71c20fe24a52022-12-22T02:49:09ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-016011436144810.1080/13880209.2022.2099429Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in miceZhongmei He0He Yu1Hong Wu2Lili Su3Kun Shi4Yan Zhao5Ying Zong6Weijia Chen7Rui Du8College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, ChinaContext Fibraurea recisa Pierre. (Menispermaceae) (FR) is a traditional Chinese medicine known as “Huangteng.” The total alkaloids of FR (AFR) are the main active ingredients. However, the pharmacological effects of AFR in the treatment of depression have not been reported.Objectives This study investigates the antidepressant effects of AFR by network pharmacology and verification experiments.Materials and methods Compound-Target-Pathway (C-P-T) network of FR and depression was constructed through network pharmacology. In vitro, HT-22 cells were treated with corticosterone (CORT) solution (0.35 mg/mL), then AFR (0.05 mg/mL) solution and inhibitor AZD6244 (14 μM/mL) or BAY11-7082 (10 μM/mL) were added, respectively. The cell viability was detected by CCK-8. In vivo, C57BL/6 mice were divided into 5 groups, namely the normal group, the CUMS group, the AFR (400 mg/kg) group, and the 2 groups that were simultaneously administered the inhibitory group AZD6244 (8 mg/kg) and BAY11-7082 (5 mg/kg). Western blotting was used to assess the expression level of the proteins.Results AFR could protect HT-22 cells from CORT-induced damage and increase the cell viability from 49.12 ± 3.4% to 87.26 ± 1.5%. Moreover, AFR significantly increased the levels of BDNF (1.3, 1.4-fold), p-ERK (1.4, 1.2-fold) and p-CERB (1.6, 1.3-fold), and decreased the levels of NLRP3 (11.3%, 31.6%), ASC (19.2%, 34.2%) and caspase-1 (18.0%, 27.6%) in HT-22 cells and the hippocampus, respectively.Discussion and conclusions AFR can improve depressive-like behaviours and can develop drugs for depression treatment. Further studies are needed to validate its potential in clinical medicine.https://www.tandfonline.com/doi/10.1080/13880209.2022.2099429CUMS modelnetwork pharmacologyBDNF-MEK/ERK signalling pathwayNLRP3/caspase-1 signalling pathway
spellingShingle Zhongmei He
He Yu
Hong Wu
Lili Su
Kun Shi
Yan Zhao
Ying Zong
Weijia Chen
Rui Du
Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
Pharmaceutical Biology
CUMS model
network pharmacology
BDNF-MEK/ERK signalling pathway
NLRP3/caspase-1 signalling pathway
title Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
title_full Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
title_fullStr Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
title_full_unstemmed Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
title_short Antidepressant effects of total alkaloids of Fibraurea recisa on improving corticosterone-induced apoptosis of HT-22 cells and chronic unpredictable mild stress-induced depressive-like behaviour in mice
title_sort antidepressant effects of total alkaloids of fibraurea recisa on improving corticosterone induced apoptosis of ht 22 cells and chronic unpredictable mild stress induced depressive like behaviour in mice
topic CUMS model
network pharmacology
BDNF-MEK/ERK signalling pathway
NLRP3/caspase-1 signalling pathway
url https://www.tandfonline.com/doi/10.1080/13880209.2022.2099429
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