Cepharanthine promotes the effect of dexmedetomidine on the deposition of β-amyloid in the old age of the senile dementia rat model by regulating inflammasome expression

Abstract

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.

Pharmacological Activity of Cepharanthine

“…It has been shown that biphasic amyloidotic symmetrical papular lesions (amyloid moss) were significantly flattened after 6 months of topical treatment with cepharanthine [ 225 ]. Cepharanthine was able to selectively inhibit the binding of β-amyloid oligomers to EphB2 [ 226 ] and improve the deposition of β-amyloid (Aβ) and NLRP3 [ 227 ], which may be a potential treatment for Alzheimer’s disease. In a rat model of Alzheimer’s disease, cepharanthine was also found to improve β-amyloid (Aβ) deposition.…”

“…In a rat model of Alzheimer’s disease, cepharanthine was also found to improve β-amyloid (Aβ) deposition. Moreover, its joint use with dexmedetomidine (DEM) improved symptoms in neurological function scores and cognitive function in Alzheimer’s rats [ 227 ].…”

“…It may also potentially be used for the treatment of late-onset neurodegenerative neuromuscular diseases by inhibiting the release of cytokines [ 221 ], which can bind to G-quadruplex nucleic acid structures, providing insight into the regulation of telomeric RNA and telomerase activity [ 215 ]. Moreover, it can also inhibit endothelial hyperplasia [ 216 , 217 ], treat venomous snake bites [ 55 , 56 , 57 , 58 , 59 ], treat amyloidosis [ 224 , 225 , 227 , 261 ], exert potential anti-atherosclerotic effects [ 169 ], ameliorate sickle-cell anemia [ 192 , 222 , 223 ], and be a potential drug for Alzheimer’s disease [ 98 , 227 ].…”

The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies

“…Dexmedetomidine improved cognitive function in AD mice by increasing miR-129 expression, which targets YAP1 and distrurbs its interaction with JAG1, resulting in decreased YAP1 and JAG1 expression, leading to suppressed oxidative stress and neuronal apoptosis (Sun et al, 2020). In rats with senile dementia, the combination of cepharantine and dexmedetomidine provided a synergistic neuroprotective effect by reducing β-amyloid deposition, inflammation, and oxidative stress, via inhibiting the NLRP3-apoptotic signalling pathway (Wu et al, 2019).…”

The Bis(1,2,3,4-tetrahydroisoquinoline) Alkaloids Cepharanthine and Berbamine Are Ligands of SK Channels

“…50 Cepharanthine also displayed cognitive enhancing properties, especially when associated with dexmedetomidine. 51 Rats of a senile dementia model receiving cepharanthine alone or in combination scored higher in assays of cognitive and neurological functions.…”