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...
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BMC
2020-02-01
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Series: | Molecular Brain |
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Online Access: | https://doi.org/10.1186/s13041-020-0560-2 |
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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 |
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institution | Directory Open Access Journal |
issn | 1756-6606 |
language | English |
last_indexed | 2024-12-14T21:08:18Z |
publishDate | 2020-02-01 |
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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 |
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