Anxiolytic effects of Formononetin in an inflammatory pain mouse model

Abstract Chronic pain is commonly accompanied with anxiety disorder, which complicates treatment. In this study, we investigated the analgesic and anxiolytic effects of Formononetin (FMNT), an active component of traditional Chinese medicine red clover (Trifolium pratense L.) that is capable of prot...

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Main Authors: Xin-shang Wang, Shao-yu Guan, An Liu, Jiao Yue, Li-ning Hu, Kun Zhang, Liu-kun Yang, Liang Lu, Zhen Tian, Ming-gao Zhao, Shui-bing Liu
Format: Article
Language:English
Published: BMC 2019-04-01
Series:Molecular Brain
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13041-019-0453-4
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author Xin-shang Wang
Shao-yu Guan
An Liu
Jiao Yue
Li-ning Hu
Kun Zhang
Liu-kun Yang
Liang Lu
Zhen Tian
Ming-gao Zhao
Shui-bing Liu
author_facet Xin-shang Wang
Shao-yu Guan
An Liu
Jiao Yue
Li-ning Hu
Kun Zhang
Liu-kun Yang
Liang Lu
Zhen Tian
Ming-gao Zhao
Shui-bing Liu
author_sort Xin-shang Wang
collection DOAJ
description Abstract Chronic pain is commonly accompanied with anxiety disorder, which complicates treatment. In this study, we investigated the analgesic and anxiolytic effects of Formononetin (FMNT), an active component of traditional Chinese medicine red clover (Trifolium pratense L.) that is capable of protecting neurons from N-methyl-D-aspartate (NMDA)-evoked excitotoxic injury, on mice suffering from complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain. The results show that FMNT administration significantly reduces anxiety-like behavior but does not affect the nociceptive threshold in CFA-injected mice. The treatment reverses the upregulation of NMDA, GluA1, and GABAA receptors, as well as PSD95 and CREB in the basolateral amygdala (BLA). The effects of FMNT on NMDA receptors and CREB binding protein (CBP) were further confirmed by the potential structure combination between these compounds, which was analyzed by in silico docking technology. FMNT also inhibits the activation of the NF-κB signaling pathway and microglia in the BLA of mice suffering from chronic inflammatory pain. Therefore, the anxiolytic effects of FMNT are partially due to the attenuation of inflammation and neuronal hyperexcitability through the inhibition of NMDA receptor and CBP in the BLA.
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spelling doaj.art-5dab2c23030e42e994a7d3a9174d089e2022-12-22T01:04:54ZengBMCMolecular Brain1756-66062019-04-0112111210.1186/s13041-019-0453-4Anxiolytic effects of Formononetin in an inflammatory pain mouse modelXin-shang Wang0Shao-yu Guan1An Liu2Jiao Yue3Li-ning Hu4Kun Zhang5Liu-kun Yang6Liang Lu7Zhen Tian8Ming-gao Zhao9Shui-bing Liu10Department of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical UniversityAbstract Chronic pain is commonly accompanied with anxiety disorder, which complicates treatment. In this study, we investigated the analgesic and anxiolytic effects of Formononetin (FMNT), an active component of traditional Chinese medicine red clover (Trifolium pratense L.) that is capable of protecting neurons from N-methyl-D-aspartate (NMDA)-evoked excitotoxic injury, on mice suffering from complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain. The results show that FMNT administration significantly reduces anxiety-like behavior but does not affect the nociceptive threshold in CFA-injected mice. The treatment reverses the upregulation of NMDA, GluA1, and GABAA receptors, as well as PSD95 and CREB in the basolateral amygdala (BLA). The effects of FMNT on NMDA receptors and CREB binding protein (CBP) were further confirmed by the potential structure combination between these compounds, which was analyzed by in silico docking technology. FMNT also inhibits the activation of the NF-κB signaling pathway and microglia in the BLA of mice suffering from chronic inflammatory pain. Therefore, the anxiolytic effects of FMNT are partially due to the attenuation of inflammation and neuronal hyperexcitability through the inhibition of NMDA receptor and CBP in the BLA.http://link.springer.com/article/10.1186/s13041-019-0453-4InflammationChronic painAnxietyFormononetinAmygdalaNMDA
spellingShingle Xin-shang Wang
Shao-yu Guan
An Liu
Jiao Yue
Li-ning Hu
Kun Zhang
Liu-kun Yang
Liang Lu
Zhen Tian
Ming-gao Zhao
Shui-bing Liu
Anxiolytic effects of Formononetin in an inflammatory pain mouse model
Molecular Brain
Inflammation
Chronic pain
Anxiety
Formononetin
Amygdala
NMDA
title Anxiolytic effects of Formononetin in an inflammatory pain mouse model
title_full Anxiolytic effects of Formononetin in an inflammatory pain mouse model
title_fullStr Anxiolytic effects of Formononetin in an inflammatory pain mouse model
title_full_unstemmed Anxiolytic effects of Formononetin in an inflammatory pain mouse model
title_short Anxiolytic effects of Formononetin in an inflammatory pain mouse model
title_sort anxiolytic effects of formononetin in an inflammatory pain mouse model
topic Inflammation
Chronic pain
Anxiety
Formononetin
Amygdala
NMDA
url http://link.springer.com/article/10.1186/s13041-019-0453-4
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