The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Volnova, Anna; Tsytsarev, Vassiliy; Ganina, Olga G.; Vélez-Crespo, Grace E.; Alves, Janaina Maria; Ignashchenkova, Alla; Inyushin, Mikhail

doi:10.3390/ijms23020663

Cited by 25 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was previously reported that CBX can exert a potential anti-inflammatory and neuroprotective effect against AD. The major concern is that CBX cannot penetrate the BBB ( Leshchenko et al, 2006 ; Volnova and Tsytsarev, 2022 ). Thereby, in this study, a single ICV injection of CBX was administrated to LPS-induced AD inflammatory rats.…”

Section: Discussionmentioning

confidence: 99%

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

et al. 2023

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.

show abstract

Section: Discussionmentioning

confidence: 99%

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Several studies have proposed that gap junctions play a key role in the synchronization of neuronal circuits. Hence, it has been postulated that enhanced gap junctional communication underlies the mechanism involved in both the generation and maintenance of seizures [ 53 , 54 , 55 ]. Studies in human fetal skin fibroblasts and in rat liver epithelial cells show that TAL enhanced the gap junctional, which correlates to a teratogenic effect [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

Cumbres-Vargas

Zamudio

Pichardo-Macías

et al. 2023

IJMS

View full text Add to dashboard Cite

Thalidomide (TAL) has shown potential therapeutic effects in neurological diseases like epilepsy. Both clinical and preclinical studies show that TAL may act as an antiepileptic drug and as a possible treatment against disease development. However, the evidence for these effects is limited. Therefore, the antiepileptogenic and anti-inflammatory effects of TAL were evaluated herein. Sprague Dawley male rats were randomly allocated to one of five groups (n = 18 per group): control (C); status epilepticus (SE); SE-TAL (25 mg/kg); SE-TAL (50 mg/kg); and SE-topiramate (TOP; 60mg/kg). The lithium-pilocarpine model was used, and one day after SE induction the rats received pharmacological treatment for one week. The brain was obtained, and the hippocampus was micro-dissected 8, 18, and 28 days after SE. TNF-α, IL-6, and IL-1β concentrations were quantified. TOP and TAL (50 mg/kg) increased the latency to the first of many spontaneous recurrent seizures (SRS) and decreased SRS frequency, as well as decreasing TNF-α and IL-1β concentrations in the hippocampus. In conclusion, the results showed that both TAL (50 mg/kg) and TOP have anti-ictogenic and antiepileptogenic effects, possibly by decreasing neuroinflammation.

show abstract

“…In angiotensin II dependent hypertension, the combination of carbenoxolone and ramipril could significantly inhibit the proliferation and migration of VSMCs [ 54 ]. In addition, carbenoxolone would also exert an antiepileptic effect in vivo and vitro by regulating gap junctions between astrocytes [ 55 ]. However, the application of carbenoxolone in psoriasis needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Biomarkers of Psoriasis through Combined Multiomics Analysis

Xing

et al. 2022

Mediators of Inflammation

View full text Add to dashboard Cite

Background. Aberrant DNA methylation patterns are of increasing interest in the study of psoriasis mechanisms. This study aims to screen potential diagnostic indicators affected by DNA methylation for psoriasis based on bioinformatics using multiple machine learning algorithms and to preliminarily explore its molecular mechanisms. Methods. GSE13355, GSE14905, and GSE73894 were collected from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated region- (DMR-) genes between psoriasis and control samples were combined to obtain differentially expressed methylated genes. Subsequently, a protein-protein interaction (PPI) network was established to analyze the interaction between differentially expressed methylated genes. Moreover, the hub genes of psoriasis were screened by the least absolute shrinkage and selection operator (LASSO), Random Forest (RF), and Support Vector Machine (SVM), which were further performed single-gene gene set enrichment analysis (GSEA) to clarify the pathogenesis of psoriasis. The druggable genes were predicted using DGIdb. Finally, the expressions of hub genes in psoriasis lesions and healthy controls were detected by immunohistochemistry (IHC) and quantitative real-time PCR (RT-qPCR). Results. In this study, a total of 767 DEGs and 896 DMR-genes were obtained. Functional enrichment showed that they were significantly associated with skin development, skin barrier function, immune/inflammatory response, and cell cycle. The combined transcriptomic and DNA methylation data resulted in 33 differentially expressed methylated genes, of which GJB2 was the final identified hub gene for psoriasis, with robust diagnostic power. IHC and RT-qPCR showed that GJB2 was significantly higher in psoriasis samples than those in healthy controls. Additionally, GJB2 may be involved in the development and progression of psoriasis by disrupting the body’s immune system, mediating the cell cycle, and destroying the skin barrier, in addition to possibly inducing diseases related to the skeletal aspects of psoriasis. Moreover, OCTANOL and CARBENOXOLONE were identified as promising compounds through the DGIdb database. Conclusion. The abnormal expression of GJB2 might play a critical role in psoriasis development and progression. The genes identified in our study might serve as a diagnostic indicator and therapeutic target in psoriasis.

show abstract

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

Cited by 25 publications

References 51 publications

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

Exploration of Biomarkers of Psoriasis through Combined Multiomics Analysis

Contact Info

Product

Resources

About