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Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
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Gingerol-Enriched Ginger Extract Effects on Anxiety-like Behavior in a Neuropathic Pain Model via Colonic

Roberto Mendóza1,2, Julianna M Santos1,3, Xiaobo Liu1

  • 1Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Molecules (Basel, Switzerland)
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Ginger extract reduced anxiety-like behavior in a rat model of neuropathic pain by modulating brain gene expression and gut bacteria. This study highlights ginger

Keywords:
anxietybioactive compoundsbraincolongut–brain axismicrobiomeneuroimmuneneuropathic painpainrats

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pharmacology

Background:

  • Gut dysbiosis is increasingly linked to anxiety and depression through neuroimmune pathways.
  • Neuropathic pain (NP) can induce anxiety-like behaviors, potentially mediated by gut-brain axis alterations.
  • Ginger and its active compounds, like gingerol, possess anti-inflammatory and neuroprotective properties.

Purpose of the Study:

  • To investigate the effects of gingerol-enriched ginger (GEG) on anxiety-like behavior in a spinal nerve ligation (SNL) rat model of neuropathic pain.
  • To examine GEG's impact on neuroinflammation, neuroimmunity, neuroplasticity, neurotransmission, and neurotoxicity-associated gene expression in various brain regions.
  • To explore the correlation between GEG treatment, colonic microflora, and anxiety-like behavior.

Main Methods:

  • Male rats underwent sham surgery, SNL, or SNL treated with GEG (200 mg/kg) for 5 weeks.
  • Anxiety-like behavior was assessed using the elevated plus maze (EPM).
  • mRNA expression of target genes in different brain regions and colonic microbiome composition were analyzed using qRT-PCR and Spearman correlation.

Main Results:

  • GEG treatment significantly reduced anxiety-like behavior in SNL rats.
  • GEG modulated the expression of genes related to neuroinflammation (NRF2, LXRα, CX3CR1), neuroplasticity (PGK1, MEK1, LDHA, GPM6A, GLUT1, HIF1α), and neurotransmission (SLC1A3, GRM5, KMO, HAAO, GRIN2B, GRIN2C).
  • GEG alleviated neurotoxicity markers (SIRT1, KMO, IDO1, HAAO) and positively correlated with reduced anxiety, while increased *Bilophila* abundance correlated with higher anxiety.

Conclusions:

  • GEG supplementation mitigates anxiety-like behavior in neuropathic pain rats, partly by reducing SNL-induced inflammatory gene expression in the brain.
  • GEG influences key pathways involved in neuroplasticity, neurotransmission, and neurotoxicity, suggesting a broad neuroprotective effect.
  • The gut microbiome, particularly the abundance of *Bilophila wadsworthia*, plays a role in anxiety-like behavior associated with neuropathic pain.