The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats

Soares-Silva, Beatriz; Beserra-Filho, José Ivo Araújo; Morera, Pamela Maria Araújo; Custódio-Silva, Ana Cláudia; Maria-Macêdo, Amanda; Silva-Martins, Suellen; Alexandre-Silva, Vanessa; Silva, Sara Pereira; Silva, Regina H.; Ribeiro, Alessandra Mussi

doi:10.1016/j.npep.2021.102209

Cited by 14 publications

(8 citation statements)

References 86 publications

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“…One advantage of bicuculline is the ability to induce seizures in multiple models from C. elegans to cats [ 134 , 135 , 136 ], providing a clear translational path from target identification in aquatic organisms to mammals. In rats, natural product screens identified sakuranetin and melittin as protective against bicuculline-induced seizures [ 137 , 138 ]. However, exposure to bicuculline does not cause significantly different electrical recordings than those generated from other chemically induced seizures [ 134 ].…”

Section: Current Aquatic Vertebrate Seizure Modelsmentioning

confidence: 99%

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery

Williams¹,

Mruk²

2022

IJMS

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Epilepsy is an international public health concern that greatly affects patients’ health and lifestyle. About 30% of patients do not respond to available therapies, making new research models important for further drug discovery. Aquatic vertebrates present a promising avenue for improved seizure drug screening and discovery. Zebrafish (Danio rerio) and African clawed frogs (Xenopus laevis and tropicalis) are increasing in popularity for seizure research due to their cost-effective housing and rearing, similar genome to humans, ease of genetic manipulation, and simplicity of drug dosing. These organisms have demonstrated utility in a variety of seizure-induction models including chemical and genetic methods. Past studies with these methods have produced promising data and generated questions for further applications of these models to promote discovery of drug-resistant seizure pathology and lead to effective treatments for these patients.

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Section: Current Aquatic Vertebrate Seizure Modelsmentioning

confidence: 99%

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery

Williams¹,

Mruk²

2022

IJMS

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“…This technique requires 15 s per measurement. Another seminal paper is the one by Leniger-Follert [21] back in 1984, which analyzed microflows during bicuculline-induced seizures [22][23][24] in anesthetized cats. In recent years, technical developments have made the measurement task more accurate and less cumbersome.…”

Section: Introductionmentioning

confidence: 99%

Velocity Estimations in Blood Microflows via Machine Learning Symmetries

Alfonso Perez,

Colchero Paetz

2024

Symmetry

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Improving velocity forecasts of blood microflows could be useful in biomedical applications. We focus on estimating the velocity of the blood in capillaries. Modeling blood microflow in capillaries is a complex process. In this paper, we use artificial intelligence techniques for this modeling: more precisely, artificial neural networks (ANNs). The selected model is able to accurately forecast the velocity, with an R2 of 0.8992 comparing the forecast with the actual velocity. A key part of ANN model creation is selecting the appropriate parameters for the ANN, such as the number of neurons, the number of layers and the type of training algorithm used. A grid approach with 327,600 simulations was used. It is shown that there are substantial, statistically significant differences when different types of ANN structures are used. It is also shown that the proposed model is robust regarding the initial random initialization of weights in the ANN. Additionally, the sensitivity of the selected models to additional noise was also tested.

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“…Previous studies demonstrated that melittin has antibacterial [ 2 ], anti-inflammatory [ 4 ], anti-arthritis [ 5 ], anti-tumor [ 6 ], and neuroprotective properties [ 7 – 9 ]. The neuroprotective effects against neurological disorders mainly included enhancing motor performance [ 10 ] and protecting neurons, inhibiting oxidative stress and alleviating memory impairments [ 7 ], decreasing neuroinflammation [ 9 ], anticonvulsant potential [ 11 ], etc. Few studies have examined the potential application and benefit of melittin for stroke.…”

Section: Introductionmentioning

confidence: 99%

“…Recent In vivo and In vitro investigations have revealed that melittin conveys neuroprotective and organ-protective influences in neurodegenerative diseases, acting through anti-apoptotic and anti-inflammatory pathways by hindering the NF-κB signaling pathway [ 11 , 28 ]. Furthermore, melittin has been observed to manifest anti-inflammatory properties in BV-2 microglia by diminishing levels of nitric oxide and inducible nitric oxide synthase, thus obstructing LPS-induced NF-κB activation [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Melittin Against Cerebral Ischemia and Inflammatory Injury via Upregulation of MCPIP1 to Suppress NF-κB Activation In Vivo and In Vitro

Xing,

Zhang,

Fan

et al. 2023

Neurochem Res

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Melittin, a principal constituent of honeybee venom, exhibits diverse biological effects, encompassing anti-inflammatory capabilities and neuroprotective actions against an array of neurological diseases. In this study, we probed the prospective protective influence of melittin on cerebral ischemia, focusing on its anti-inflammatory activity. Mechanistically, we explored whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as ZC3H12A), a recently identified zinc-finger protein, played a role in melittin-mediated anti-inflammation and neuroprotection. Male C57/BL6 mice were subjected to distal middle cerebral artery occlusion to create a focal cerebral cortical ischemia model, with melittin administered intraperitoneally. We evaluated motor functions, brain infarct volume, cerebral blood flow, and inflammatory marker levels within brain tissue, employing quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and western blotting. In vitro, an immortalized BV-2 microglia culture was stimulated with lipopolysaccharide (LPS) to establish an inflammatory cell model. Post-melittin exposure, cell viability, and cytokine expression were examined. MCPIP1 was silenced using siRNA in LPS-induced BV-2 cells, with the ensuing nuclear translocation of nuclear factor-κB assessed through cellular immunofluorescence. In vivo, melittin enhanced motor functions, diminished infarction, fostered blood flow restoration in ischemic brain regions, and markedly inhibited the expression of inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and nuclear factor-κB). In vitro, melittin augmented MCPIP1 expression in LPS-induced BV-2 cells and ameliorated inflammation-induced cell death. The neuroprotective effect conferred by melittin was attenuated upon MCPIP1 knockdown. Our findings establish that melittin-induced tolerance to ischemic injury is intrinsically linked with its anti-inflammatory capacity. Moreover, MCPIP1 is, at the very least, partially implicated in this process.

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The bee venom active compound melittin protects against bicuculline-induced seizures and hippocampal astrocyte activation in rats

Cited by 14 publications

References 86 publications

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery

Velocity Estimations in Blood Microflows via Machine Learning Symmetries

Neuroprotective Effects of Melittin Against Cerebral Ischemia and Inflammatory Injury via Upregulation of MCPIP1 to Suppress NF-κB Activation In Vivo and In Vitro

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