1. Anxiolytic effects of Formononetin in an inflammatory pain mouse model.
- Author
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Wang XS, Guan SY, Liu A, Yue J, Hu LN, Zhang K, Yang LK, Lu L, Tian Z, Zhao MG, and Liu SB
- Subjects
- Animals, Anti-Anxiety Agents pharmacology, Basolateral Nuclear Complex metabolism, Behavior, Animal drug effects, Cyclic AMP Response Element-Binding Protein metabolism, Disease Models, Animal, Freund's Adjuvant, Isoflavones chemistry, Isoflavones pharmacology, Male, Mice, Inbred C57BL, Microglia drug effects, Microglia metabolism, Microglia pathology, Models, Molecular, NF-kappa B metabolism, NF-kappa B pharmacokinetics, Pain drug therapy, Receptors, GABA metabolism, Receptors, N-Methyl-D-Aspartate chemistry, Receptors, N-Methyl-D-Aspartate metabolism, Signal Transduction, Up-Regulation drug effects, Anti-Anxiety Agents therapeutic use, Anxiety therapy, Inflammation pathology, Isoflavones therapeutic use
- 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 GABA
A 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.- Published
- 2019
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