Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder

Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder...

Full description

Bibliographic Details
Main Authors: Chao Liu, Zhenhao Ying, Zifa Li, Long Zhang, Xin Li, Wenbo Gong, Jiang Sun, Xuejing Fan, Ke Yang, Xingchen Wang, Sheng Wei, Ning Dong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.772576/full
_version_ 1818346366916624384
author Chao Liu
Zhenhao Ying
Zifa Li
Zifa Li
Zifa Li
Long Zhang
Xin Li
Wenbo Gong
Jiang Sun
Xuejing Fan
Ke Yang
Xingchen Wang
Xingchen Wang
Sheng Wei
Sheng Wei
Sheng Wei
Ning Dong
Ning Dong
author_facet Chao Liu
Zhenhao Ying
Zifa Li
Zifa Li
Zifa Li
Long Zhang
Xin Li
Wenbo Gong
Jiang Sun
Xuejing Fan
Ke Yang
Xingchen Wang
Xingchen Wang
Sheng Wei
Sheng Wei
Sheng Wei
Ning Dong
Ning Dong
author_sort Chao Liu
collection DOAJ
description Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood.Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway.Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting.Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior.Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.
first_indexed 2024-12-13T17:17:08Z
format Article
id doaj.art-90ac80cba309471fa2465c4807479440
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-12-13T17:17:08Z
publishDate 2021-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-90ac80cba309471fa2465c48074794402022-12-21T23:37:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.772576772576Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety DisorderChao Liu0Zhenhao Ying1Zifa Li2Zifa Li3Zifa Li4Long Zhang5Xin Li6Wenbo Gong7Jiang Sun8Xuejing Fan9Ke Yang10Xingchen Wang11Xingchen Wang12Sheng Wei13Sheng Wei14Sheng Wei15Ning Dong16Ning Dong17The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaSchool of Rehabilitation Science, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaShandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaThe First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaCollege of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaThe First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaThe First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaCollege of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaCollege of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaDepartment of Neurology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaThe Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaExperimental Center, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaKey Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaShandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaDepartment of Neurology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaThe Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Ji’nan, ChinaBackground: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood.Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway.Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting.Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior.Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.https://www.frontiersin.org/articles/10.3389/fphar.2021.772576/fullGeneralized anxiety disorderDZXYShippocampusNotchneuron regeneration
spellingShingle Chao Liu
Zhenhao Ying
Zifa Li
Zifa Li
Zifa Li
Long Zhang
Xin Li
Wenbo Gong
Jiang Sun
Xuejing Fan
Ke Yang
Xingchen Wang
Xingchen Wang
Sheng Wei
Sheng Wei
Sheng Wei
Ning Dong
Ning Dong
Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
Frontiers in Pharmacology
Generalized anxiety disorder
DZXYS
hippocampus
Notch
neuron regeneration
title Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
title_full Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
title_fullStr Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
title_full_unstemmed Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
title_short Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder
title_sort danzhi xiaoyao powder promotes neuronal regeneration by downregulating notch signaling pathway in the treatment of generalized anxiety disorder
topic Generalized anxiety disorder
DZXYS
hippocampus
Notch
neuron regeneration
url https://www.frontiersin.org/articles/10.3389/fphar.2021.772576/full
work_keys_str_mv AT chaoliu danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT zhenhaoying danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT zifali danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT zifali danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT zifali danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT longzhang danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT xinli danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT wenbogong danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT jiangsun danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT xuejingfan danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT keyang danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT xingchenwang danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT xingchenwang danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT shengwei danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT shengwei danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT shengwei danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT ningdong danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder
AT ningdong danzhixiaoyaopowderpromotesneuronalregenerationbydownregulatingnotchsignalingpathwayinthetreatmentofgeneralizedanxietydisorder