Aim of the study: The present study evaluates the synergistic effect of cepharanthine (CP) with dexmedetomidine (DEM) on the deposition of β-amyloid (Aβ) in the brain tissue of senile dementia (SD) rats.
Material and methods: Senile dementia was induced by injecting D-gal intraperitoneally 60 mg/kg/day for six weeks and Aβ1-42 (5 µl) intracranially. The effect of cepharanthine and dexmedetomidine was estimated by determining the cognitive function and neurological function score. Moreover, mediators of inflammation, parameters of oxidative stress and reactive oxygen species (ROS) were determined in the brain tissue of senile dementia rats. Mitochondrial membrane permeability and deposition of Aβ1-42 was estimated in senile dementia rats. Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) was performed for the expression of proteins and genes in the brain tissue of senile dementia rats.
Results: Data of the study reveal that cepharanthine alone and in combination with dexmedetomidine improves the neurological function score and cognitive function in SD rats. Moreover, parameters of oxidative stress, inflammatory mediators and production of ROS in CP, DEM and CP + DEM treated groups were compared to the SD group of rats. Treatment with CP, DEM and CP + DEM ameliorates the altered expression of NLRP3 pathway and deposition of Aβ in the brain tissue of SD rats.
Conclusions: In conclusion, data reveal that cepharanthine ameliorates the deposition of Aβ and NLRP3 pathway in SD rats. Moreover, cepharanthine treatment with dexmedetomidine shows the synergistic effect against the aged SD rat model.
Keywords: dementia; dexmedetomidine; inflammasomes; β-amyloid; cepharanthine.