Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model

Abstract Anxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. Scopoletin (SP), a main active compound in Angelica dahurica, is traditionally used f...

Full description

Bibliographic Details
Main Authors: Li Luo, Ting Sun, Le Yang, An Liu, Qing-qing Liu, Qin-qin Tian, Yan Wang, Ming-gao Zhao, Qi Yang
Format: Article
Language:English
Published: BMC 2020-02-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-020-0560-2
_version_ 1818451507791527936
author Li Luo
Ting Sun
Le Yang
An Liu
Qing-qing Liu
Qin-qin Tian
Yan Wang
Ming-gao Zhao
Qi Yang
author_facet Li Luo
Ting Sun
Le Yang
An Liu
Qing-qing Liu
Qin-qin Tian
Yan Wang
Ming-gao Zhao
Qi Yang
author_sort Li Luo
collection DOAJ
description Abstract Anxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. Scopoletin (SP), a main active compound in Angelica dahurica, is traditionally used for the treatment of headache, rhinitis, pain, and other conditions. Here, we evaluated the effects of SP in a mouse model of complete Freund’s adjuvant (CFA)-induced chronic inflammation anxiety. SP (2.0, 10.0, 50.0 mg/kg) administration for 2 weeks dose-dependently ameliorated CFA-induced anxiety-like behaviors in the open field test and elevated plus maze test. Moreover, we found that SP treatment inhibited microglia activation and decreased both peripheral and central IL-1β, IL-6, and TNF-α levels in a dose-dependent manner. Additionally, the imbalance in excitatory/inhibitory receptors and neurotransmitters in the basolateral nucleus after CFA injection was also modulated by SP administration. Our findings indicate that the inhibition of the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways involving anti-inflammatory activities and regulation of the excitatory/inhibitory balance can be attributed to the anxiolytic effects of SP. Moreover, our molecular docking analyses show that SP also has good affinity for gamma-aminobutyric acid (GABA) transaminase and GABAA receptors. Therefore, these results suggest that SP could be a candidate compound for anxiolytic therapy and for use as a structural base for developing new drugs.
first_indexed 2024-12-14T21:08:18Z
format Article
id doaj.art-3518a97101e548deb1fe1853c5599a9e
institution Directory Open Access Journal
issn 1756-6606
language English
last_indexed 2024-12-14T21:08:18Z
publishDate 2020-02-01
publisher BMC
record_format Article
series Molecular Brain
spelling doaj.art-3518a97101e548deb1fe1853c5599a9e2022-12-21T22:47:20ZengBMCMolecular Brain1756-66062020-02-0113111310.1186/s13041-020-0560-2Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse modelLi Luo0Ting Sun1Le Yang2An Liu3Qing-qing Liu4Qin-qin Tian5Yan Wang6Ming-gao Zhao7Qi Yang8Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Chemistry, School of Pharmacy, Fourth Military Medical UniversityDepartment of Gastroenterology and Endoscopy Center, No. 986 Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityPrecision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityAbstract Anxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. Scopoletin (SP), a main active compound in Angelica dahurica, is traditionally used for the treatment of headache, rhinitis, pain, and other conditions. Here, we evaluated the effects of SP in a mouse model of complete Freund’s adjuvant (CFA)-induced chronic inflammation anxiety. SP (2.0, 10.0, 50.0 mg/kg) administration for 2 weeks dose-dependently ameliorated CFA-induced anxiety-like behaviors in the open field test and elevated plus maze test. Moreover, we found that SP treatment inhibited microglia activation and decreased both peripheral and central IL-1β, IL-6, and TNF-α levels in a dose-dependent manner. Additionally, the imbalance in excitatory/inhibitory receptors and neurotransmitters in the basolateral nucleus after CFA injection was also modulated by SP administration. Our findings indicate that the inhibition of the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways involving anti-inflammatory activities and regulation of the excitatory/inhibitory balance can be attributed to the anxiolytic effects of SP. Moreover, our molecular docking analyses show that SP also has good affinity for gamma-aminobutyric acid (GABA) transaminase and GABAA receptors. Therefore, these results suggest that SP could be a candidate compound for anxiolytic therapy and for use as a structural base for developing new drugs.https://doi.org/10.1186/s13041-020-0560-2AnxietyInflammationGlutamateGABAScopoletinAmygdala
spellingShingle Li Luo
Ting Sun
Le Yang
An Liu
Qing-qing Liu
Qin-qin Tian
Yan Wang
Ming-gao Zhao
Qi Yang
Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
Molecular Brain
Anxiety
Inflammation
Glutamate
GABA
Scopoletin
Amygdala
title Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
title_full Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
title_fullStr Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
title_full_unstemmed Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
title_short Scopoletin ameliorates anxiety-like behaviors in complete Freund’s adjuvant-induced mouse model
title_sort scopoletin ameliorates anxiety like behaviors in complete freund s adjuvant induced mouse model
topic Anxiety
Inflammation
Glutamate
GABA
Scopoletin
Amygdala
url https://doi.org/10.1186/s13041-020-0560-2
work_keys_str_mv AT liluo scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT tingsun scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT leyang scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT anliu scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT qingqingliu scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT qinqintian scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT yanwang scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT minggaozhao scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel
AT qiyang scopoletinamelioratesanxietylikebehaviorsincompletefreundsadjuvantinducedmousemodel