Dextran Sulphate of Sodium-induced colitis in mice: antihyperalgesic effects of ethanolic extract of Citrus reticulata and potential damage to the central nervous system

Abstract

Citrus species are widely related to antihyperalgesic and anti-inflammatory effects. The aim of this study was to investigate if treatment with ethanolic extract from peels of mature Citrus reticulata Blanco causes antihyperalgesic effects on the referred mechanical hyperalgesia in a model of dextran sulphate of sodium (DSS)-induced colitis in mice, as well as the possible oxidative damage in different regions of the brain induced by its inflammatory reaction. Antihyperalgesia (30 to 300 mg/kg) was investigated by behavioral response (frequency of response to von Frey filament stimulation) in Swiss mice, while damage to central nervous system was investigated through techniques that evaluated oxidative stress using male black C57 BL6 mice (n=8). Treatment of the animals with the extract (100 mg/kg) from days 3 to 5 after colitis induction reduced referred the mechanical hyperalgesia (32.6 ± 5.1) in relation to the control group (57.4 ± 2.0). Levels of lipid peroxidation or carbonyl proteins were augmented in colitis-induced animals in relation to the disease group. These results indicated an antihyperalgesic effect of the studied extract and a potential impairment of the central nervous system functioning caused by inflammation during colitis, which could be related to mental disorders observed in patients suffering of this pathology.

Hesperidin modulates dextran sulfate sodium‐induced ulcerative colitis in rats: Targeting sphingosine kinase‐1‐ sphingosine 1 phosphate signaling pathway, mitochondrial biogenesis, inflammation, and apoptosis

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Neuroinflammatory Remodeling of the Anterior Cingulate Cortex as a Key Driver of Mood Disorders in Gastrointestinal Disease and Disorders

“…reduced tight junction protein (occludin and claudin-5) mRNA in the hippocampus and cortex of DSS-treated mice relative to controls; increased cleaved caspase 3 (marker of apoptosis) mRNA in cortex of DSS-treated mice relative to controls DSS ( 1 cycle) in C57Bl/6 male mice -increased markers of oxidative stress in the PFC and hippocampus(276) DSS (1 cycle) in C57Bl/6J male and female mice -increased anxiety and reduced locomotion in male and female mice (EPM, OFT) -thermal and mechanism hypersensitivity in male mice -increased CNS excitability (seizure onset time when exposed to KA seizing agent)(277)DSS (1 cycle) in male Wistar rats, during disease and resolution/recovery phase -reduced locomotion and increased anxiety in active, but not recovery phase (open field test) -reduced sucrose consumption during active and recovery phase (sucrose preference test) -reduced marble burying in recovery phase -depression in recovery phase (FST) -increased anxiety in recovery phase (light/dark box, EPM) -increased IL-6 and iNOS mRNA in the cerebral cortex of rats during active disease and recovery phase -increased iNOS, 3-NT, and IBA1 immunoreactivity in median eminence in active and recovery phase -Increase in ventricular volume in active and recovery phase -reduced T2 relaxation times in DSS-treated animals in the cingulate, sensory, and motor cortices -increase in FosB immunoreactivity in DSS-treated mice(246) DSS (4 cycles) in C57Bl/6 female mice -increased volume, # reactive microglia, reduced neurons in peri-lesion area 7d after a stroke in DSStreated mice -reduced ratio of anti-inflammatory/proinflammatory microglia 3 and 7d post stroke in DSS treated mice -increased infiltration of gut-derived T-cells in meninges, and peripherally derived T cells in the peri-lesion area of DSS-treated mice (214) -peripheral macrophage depletion suppressed T-cell infiltration in the peri-lesion area DSS (1 cycle) in C57Bl/6 male and female mice, at peak disease and resolution of colitis -reduced latency to food interactions (hyponeophagia) and reduced time spent grooming 2.5 weeks post DSS exposure -increased depressive-like behaviour (FST and TST) during recovery phase 3.5 weeks post DSS exposure Increased eIPSCs and lower eIPSC threshold in pyramidal cells of the CA1 area of the hippocampus -increased IL-1b mRNA in hippocampus -increased trafficking of leukocytes in PFC (249) DSS (1 cycle) in male kunming mice -increased anxiety (EPM, OFT) -reduced protein expression of CRH in the hypothalamus (Models of Crohn's Disease Effect on Behaviour Effect on Brain/CNS Reference TNBS colitis in Sprague-Dawley rats -increased mRNA of CRF in mPVN and SON of TNBS-treated rats (279) TNBS colitis in Sprague-Dawley adult male rats…”