Anxiolytic effects of Formononetin in an inflammatory pain mouse model

Autor: Ming-gao Zhao, An Liu, Kun Zhang, Zhen Tian, Shui-bing Liu, Xin-shang Wang, Shao-yu Guan, Li-ning Hu, Jiao Yue, Liang Lu, Liu-kun Yang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Models
Molecular
0301 basic medicine
Freund's Adjuvant
Chronic pain
Pharmacology
Anxiety
lcsh:RC346-429
0302 clinical medicine
Cyclic AMP Response Element-Binding Protein
Behavior
Animal
biology
Basolateral Nuclear Complex
GABAA receptor
NF-kappa B
Amygdala
Up-Regulation
medicine.anatomical_structure
NMDA receptor
Microglia
Signal Transduction
medicine.drug_class
Analgesic
Pain
CREB
Receptors
N-Methyl-D-Aspartate
Anxiolytic
03 medical and health sciences
Cellular and Molecular Neuroscience
Receptors
GABA
medicine
Animals
CREB-binding protein
Molecular Biology
lcsh:Neurology. Diseases of the nervous system
Inflammation
Formononetin
business.industry
Research
medicine.disease
Isoflavones
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Anti-Anxiety Agents
nervous system
NMDA
biology.protein
business
030217 neurology & neurosurgery
Basolateral amygdala
Zdroj: Molecular Brain, Vol 12, Iss 1, Pp 1-12 (2019)
Molecular Brain
ISSN: 1756-6606
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13041-019-0453-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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