Sagar Mahawar , Debarati Rakshit , Inklisan Patel , Swati Kailas Gore , Srijita Sen , Om Prakash Ranjan , Awanish Mishra
{"title":"甲壳素载体壳聚糖纳米粒子可改善皮质类药物诱发的小鼠颞叶癫痫及相关神经行为改变：ROS/TNF-α-NLRP3炎性体通路的作用","authors":"Sagar Mahawar , Debarati Rakshit , Inklisan Patel , Swati Kailas Gore , Srijita Sen , Om Prakash Ranjan , Awanish Mishra","doi":"10.1016/j.nano.2024.102752","DOIUrl":null,"url":null,"abstract":"<div><p>Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP.</p><p>Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated.</p><p>The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"59 ","pages":"Article 102752"},"PeriodicalIF":4.2000,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway\",\"authors\":\"Sagar Mahawar , Debarati Rakshit , Inklisan Patel , Swati Kailas Gore , Srijita Sen , Om Prakash Ranjan , Awanish Mishra\",\"doi\":\"10.1016/j.nano.2024.102752\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP.</p><p>Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated.</p><p>The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.</p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":\"59 \",\"pages\":\"Article 102752\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-05-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963424000212\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963424000212","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway
Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP.
Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated.
The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.
期刊介绍：
The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.
Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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