Neuroprotection impact of biochanin A against pentylenetetrazol-kindled mice: Targeting NLRP3 inflammasome/TXNIP pathway and autophagy modulation

El‐Sayed, Rehab M.; Fawzy, Mohamed N; Zaki, Hala F.; El-Haleim, Enas A Abd

doi:10.1016/j.intimp.2023.109711

Cited by 13 publications

(9 citation statements)

References 87 publications

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“…Promising results have been demonstrated with a natural isoflavone, biochanin A. This natural agent restored autophagy and protected against neurodegeneration [ 79 , 80 , 81 ].…”

Section: Discussionmentioning

confidence: 99%

Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy

Alshaman,

Kolieb,

El-Sayed

et al. 2024

Biomedicines

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Diabetic retinopathy (DR) is a debilitating diabetic disorder of the retinal microvasculature and the main cause of avoidable blindness in old people. Hesperetin is a plant flavanone largely abundant in citrus species with neuroprotective properties in animal models. This study aimed to explore the neuroprotective and autophagy-enhancing effect of hesperetin in rats with DR. Twenty-four male rats were utilized and allocated to groups: (i) the vehicle group, (ii) DR group and (iii–iv) the DR + hesperetin (50 and 100 mg/kg) groups. Treatment with hesperetin continued for 6 weeks. After the rats were euthanized, their eyes were dissected to detect the biochemical and histological changes in the retinas. Quantification of autophagy markers, beclin 1/LC3/p62, and inflammation markers was performed. Histopathologic changes were investigated after staining with hematoxylin and eosin and periodic acid–Schiff (PAS). Results demonstrated that hesperetin decreased the PAS staining in diabetic rats and attenuated histopathological changes and restored retinal organization and thickness of layers in hematoxylin and eosin staining. Moreover, hesperetin reduced the level of mRNA expression for TNF-α (4.9-fold), IL-1β (4.15-fold), IL-6 (4.6-fold) and NFκB (5.2-fold), as well as the protein level. This was accompanied by induction of autophagy proteins, beclin 1 and LC3-II. Our results afford evidence that hesperetin is effective in alleviating the pathology of DR via suppressing the inflammatory burden and induction of autophagy. After extensive clinical examinations, hesperetin may prove to be a useful option for treatment of DR.

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“…Promising results have been demonstrated with a natural isoflavone, biochanin A. This natural agent restored autophagy and protected against neurodegeneration [ 79 , 80 , 81 ].…”

Section: Discussionmentioning

confidence: 99%

Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy

Alshaman,

Kolieb,

El-Sayed

et al. 2024

Biomedicines

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“…Furthermore, neuroinflammation is closely associated with the activity of the central nervous system's innate immune cells, particularly microglia and astrocytes (Kwon et al, 2020). Activated microglia and astrocytes are recognized as crucial factors in the hyperexcitability of neuronal networks that underlie seizures (El-Sayed et al, 2023). This functional activation leads to alterations in the expression of intracellular metabolites, transporters, and membrane proteins (Vezzani et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Astragalus polysaccharides ameliorate epileptogenesis, cognitive impairment, and neuroinflammation in a pentylenetetrazole-induced kindling mouse model

Lu,

Lin,

et al. 2024

Front. Pharmacol.

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Background: Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that Astragalus polysaccharides (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism.Methods: Initially, we employed pentylenetetrazol-induced seizure mice to validate APS’ effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action.Results: APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model.Conclusion: The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.

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“…Treatment with natural antioxidants such as amentoflavone and biochanin A reduced seizure susceptibility in pentylenetetrazole (PTZ)induced kindling mice. This reduction was achieved by inhibiting PTZ-induced expression of NLRP3, ASC, and caspase-1, thereby blocking neuronal apoptosis and improving cognitive performance [125,169]. Moreover, ibuprofen, a non-steroidal anti-inflammatory drug, also inhibited the expression of NLRP3, caspase-1, and IL-18 in a chronic model of PTZ-kindled epileptic rats.…”

Section: Investigating In Vivo Epilepsy Modelsmentioning

confidence: 99%

The NLRP3 Inflammasome in Neurodegenerative Disorders: Insights from Epileptic Models

Palumbo,

Carinci,

Guarino

et al. 2023

Biomedicines

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Neuroinflammation represents a dynamic process of defense and protection against the harmful action of infectious agents or other detrimental stimuli in the central nervous system (CNS). However, the uncontrolled regulation of this physiological process is strongly associated with serious dysfunctional neuronal issues linked to the progression of CNS disorders. Moreover, it has been widely demonstrated that neuroinflammation is linked to epilepsy, one of the most prevalent and serious brain disorders worldwide. Indeed, NLRP3, one of the most well-studied inflammasomes, is involved in the generation of epileptic seizures, events that characterize this pathological condition. In this context, several pieces of evidence have shown that the NLRP3 inflammasome plays a central role in the pathophysiology of mesial temporal lobe epilepsy (mTLE). Based on an extensive review of the literature on the role of NLRP3-dependent inflammation in epilepsy, in this review we discuss our current understanding of the connection between NLRP3 inflammasome activation and progressive neurodegeneration in epilepsy. The goal of the review is to cover as many of the various known epilepsy models as possible, providing a broad overview of the current literature. Lastly, we also propose some of the present therapeutic strategies targeting NLRP3, aiming to provide potential insights for future studies.

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Neuroprotection impact of biochanin A against pentylenetetrazol-kindled mice: Targeting NLRP3 inflammasome/TXNIP pathway and autophagy modulation

Cited by 13 publications

References 87 publications

Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy

Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy

Astragalus polysaccharides ameliorate epileptogenesis, cognitive impairment, and neuroinflammation in a pentylenetetrazole-induced kindling mouse model

The NLRP3 Inflammasome in Neurodegenerative Disorders: Insights from Epileptic Models

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