{"title":"仙原素通过促进线粒体自噬和抑制NLRP3炎性体激活来改善糖尿病性脑病。","authors":"Xiao-Dan Yan, Yu Yang, Wan-Ting Zhang, Qing-Quan Kong, Xi-Tong Zheng, Lin-Sen Li, Qing Yu","doi":"10.1007/s00213-025-06796-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Diabetic encephalopathy (DE) remains a severe complication of diabetes in central nervous system with limited effective therapy.</p><p><strong>Objectives: </strong>This study investigated the beneficial effect of senegenin on DE and its possible mechanisms.</p><p><strong>Methods: </strong>Type 2 diabetes mellitus mouse model and high-glucose (HG)-stimulated PC-12 cells were used as the in vivo and in vitro DE models. Learning and memory ability was evaluated by MWM test. Pathological changes in the brain tissues were determined by HE staining. Cell viability was detected by CCK-8. Mitochondrial membrane potential was measured by JC-1 probe. Target protein levels were assessed by Western blotting. Nucleotide-binding domain-like receptor protein 3 (NLRP3) expression was observed by immunofluorescent staining.</p><p><strong>Results: </strong>Cognitive impairment and obvious pathological changes were found in DE mice, which were effectively attenuated by senegenin treatment. In addition, senegenin induced mitophagy and maintained homeostasis of mitochondrial dynamics to relieve mitochondrial dysfunction. Moreover, NLRP3 inflammation activation induced by DE was inhibited by senegenin. Finally, inhibition of mitophagy counteracted senegenin-mediated inactivation of NLRP3 inflammation and neuroprotection.</p><p><strong>Conclusions: </strong>Senegenin relieved diabetic encephalopathy via inducing mitophagy to inactivate NLRP3 inflammasome. Senegenin might be an effective therapy for treating DE.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Senegenin ameliorates diabetic encephalopathy via promoting mitophagy and repressing NLRP3 inflammasome activation.\",\"authors\":\"Xiao-Dan Yan, Yu Yang, Wan-Ting Zhang, Qing-Quan Kong, Xi-Tong Zheng, Lin-Sen Li, Qing Yu\",\"doi\":\"10.1007/s00213-025-06796-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Diabetic encephalopathy (DE) remains a severe complication of diabetes in central nervous system with limited effective therapy.</p><p><strong>Objectives: </strong>This study investigated the beneficial effect of senegenin on DE and its possible mechanisms.</p><p><strong>Methods: </strong>Type 2 diabetes mellitus mouse model and high-glucose (HG)-stimulated PC-12 cells were used as the in vivo and in vitro DE models. Learning and memory ability was evaluated by MWM test. Pathological changes in the brain tissues were determined by HE staining. Cell viability was detected by CCK-8. Mitochondrial membrane potential was measured by JC-1 probe. Target protein levels were assessed by Western blotting. Nucleotide-binding domain-like receptor protein 3 (NLRP3) expression was observed by immunofluorescent staining.</p><p><strong>Results: </strong>Cognitive impairment and obvious pathological changes were found in DE mice, which were effectively attenuated by senegenin treatment. In addition, senegenin induced mitophagy and maintained homeostasis of mitochondrial dynamics to relieve mitochondrial dysfunction. Moreover, NLRP3 inflammation activation induced by DE was inhibited by senegenin. Finally, inhibition of mitophagy counteracted senegenin-mediated inactivation of NLRP3 inflammation and neuroprotection.</p><p><strong>Conclusions: </strong>Senegenin relieved diabetic encephalopathy via inducing mitophagy to inactivate NLRP3 inflammasome. Senegenin might be an effective therapy for treating DE.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-04-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-025-06796-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06796-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Senegenin ameliorates diabetic encephalopathy via promoting mitophagy and repressing NLRP3 inflammasome activation.
Rationale: Diabetic encephalopathy (DE) remains a severe complication of diabetes in central nervous system with limited effective therapy.
Objectives: This study investigated the beneficial effect of senegenin on DE and its possible mechanisms.
Methods: Type 2 diabetes mellitus mouse model and high-glucose (HG)-stimulated PC-12 cells were used as the in vivo and in vitro DE models. Learning and memory ability was evaluated by MWM test. Pathological changes in the brain tissues were determined by HE staining. Cell viability was detected by CCK-8. Mitochondrial membrane potential was measured by JC-1 probe. Target protein levels were assessed by Western blotting. Nucleotide-binding domain-like receptor protein 3 (NLRP3) expression was observed by immunofluorescent staining.
Results: Cognitive impairment and obvious pathological changes were found in DE mice, which were effectively attenuated by senegenin treatment. In addition, senegenin induced mitophagy and maintained homeostasis of mitochondrial dynamics to relieve mitochondrial dysfunction. Moreover, NLRP3 inflammation activation induced by DE was inhibited by senegenin. Finally, inhibition of mitophagy counteracted senegenin-mediated inactivation of NLRP3 inflammation and neuroprotection.
Conclusions: Senegenin relieved diabetic encephalopathy via inducing mitophagy to inactivate NLRP3 inflammasome. Senegenin might be an effective therapy for treating DE.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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