Scopoletin ameliorates anxiety-like behaviors in complete Freund\u2019s adjuvant-induced mouse model

Qing-Qing Liu,Le Yang,Yan Wang,An Liu,Li Luo,Qi Yang,Ming-Gao Zhao,Ting Sun,Qin-Qin Tian

doi:10.1186/s13041-020-0560-2

Qing-Qing Liu, Le Yang + Show 7 more

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https://doi.org/10.1186/s13041-020-0560-2

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Journal: Molecular Brain	Publication Date: Feb 4, 2020
Citations: 29	License type: open-access

Affiliation: Air Force Medical University

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.

Highlights

Anxiety disorder is highly common worldwide, with an estimated prevalence of 15% in developed countries, and seriously affects people’s life and work [1]
Compared with the control group, complete Freund’s adjuvant (CFA)-injected mice showed shorter times spent and distances traveled in the central area of the open field test (OFT) (Fig. 1a-c), which indicates anxiety-like symptoms
SP regulates inflammation by inhibiting gamma-aminobutyric acid (GABA) transaminase (GABA-T) and associated signals In order to find the reason for the dysregulation in neuronal transmission, we focused on the critical enzyme involved in GABA metabolism, GABA-T, which decreases the level of GABA in the brain while increasing the level of glutamate [29]

Summary

Introduction

Anxiety disorder is highly common worldwide, with an estimated prevalence of 15% in developed countries, and seriously affects people’s life and work [1] It is a chronic and functionally disabling condition that induces high levels of psychological stress and is characterized by cognitive symptoms, such as excessive worry and focus difficulties, as well as physiological symptoms, such as muscle tension and insomnia [1, 2]. While antidepressants and benzodiazepines are clinically useful for treating anxiety, considerable side effects, such as the risk of physical dependence, addiction, excessive sedation, and abuse, are observed in clinical practice [3, 4]. Low central gamma-aminobutyric acid (GABA) and high glutamate levels are known to result in hyperexcitation and

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