Jingyi Li, Xiufeng Wang, Yu Zhang, Min Wei, Jianqiang Qi, Dan Liu, Runhua Wu, Qin Chen, Junshan Huang
{"title":"人参皂苷Rg1通过Nrf2/HO-1通路抑制NLRP3炎性体激活和焦亡，减轻pppa诱导的小鼠失眠。","authors":"Jingyi Li, Xiufeng Wang, Yu Zhang, Min Wei, Jianqiang Qi, Dan Liu, Runhua Wu, Qin Chen, Junshan Huang","doi":"10.1007/s00213-025-06828-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to investigate the neuroprotective effects of Ginsenoside Rg1 in alleviating P-chlorophenylalanine (PCPA)-induced insomnia and explore its underlying mechanisms involving the inhibition of NOD-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and pyroptosis through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway in mice.</p><p><strong>Methods: </strong>Sprague-Dawley rats were randomly divided into five groups: control, sleep deprivation (SD, PCPA-induced insomnia), and three treatment groups receiving different doses of Ginsenoside Rg1 (low, medium, and high). Behavioral assessments included the Pentobarbital Sodium-Induced Sleep Test (PIST), Sucrose Preference Test (SPT), and Morris Water Maze (MWM). Histopathological and immunofluorescence evaluations of hippocampal tissues were performed. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure neurotransmitter levels (5-Hydroxytryptamine [5-HT], 5-Hydroxytryptophan [5-HTP], Gamma-aminobutyric acid [GABA], glutamate [GLU]) and pro-inflammatory cytokines (Tumor Necrosis Factor Alpha [TNF-α], Interleukin-6 [IL-6], Interleukin-1 beta [IL-1β], Interleukin-8 [IL-8]). In vitro, corticosterone-induced neurotoxicity in HT22 hippocampal cells was assessed, and the role of the Nrf2/HO-1 pathway was examined through molecular docking, gene silencing, and Western blot.</p><p><strong>Results: </strong>Ginsenoside Rg1 treatment significantly improved PCPA-induced insomnia symptoms in a dose-dependent manner, as evidenced by reduced sleep latency, increased sleep duration, restored sucrose preference, and improved spatial memory. Histopathological analysis revealed that Ginsenoside Rg1 mitigated neuronal damage and astrocytic activation. Neurotransmitter imbalances were corrected, and inflammation was alleviated, as reflected by reductions in pro-inflammatory cytokines and increased interleukin-10 (IL-10) levels. Mechanistically, Ginsenoside Rg1 inhibited NLRP3 inflammasome activation, pyroptosis, and reduced IL-1β and IL-8 levels in both in vivo and in vitro models. The activation of the Nrf2/HO-1 pathway was further confirmed by molecular docking, immunofluorescence, and Western blot, demonstrating that Nrf2 activation was critical for the anti-inflammatory effects of Ginsenoside Rg1.</p><p><strong>Conclusion: </strong>Ginsenoside Rg1 effectively alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis, with its neuroprotective effects mediated through the activation of the Nrf2/HO-1 pathway. These findings suggest Ginsenoside Rg1 as a potential therapeutic agent for insomnia and related neuroinflammatory conditions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ginsenoside Rg1 alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis through the Nrf2/HO-1 pathway in mice.\",\"authors\":\"Jingyi Li, Xiufeng Wang, Yu Zhang, Min Wei, Jianqiang Qi, Dan Liu, Runhua Wu, Qin Chen, Junshan Huang\",\"doi\":\"10.1007/s00213-025-06828-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>This study aims to investigate the neuroprotective effects of Ginsenoside Rg1 in alleviating P-chlorophenylalanine (PCPA)-induced insomnia and explore its underlying mechanisms involving the inhibition of NOD-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and pyroptosis through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway in mice.</p><p><strong>Methods: </strong>Sprague-Dawley rats were randomly divided into five groups: control, sleep deprivation (SD, PCPA-induced insomnia), and three treatment groups receiving different doses of Ginsenoside Rg1 (low, medium, and high). Behavioral assessments included the Pentobarbital Sodium-Induced Sleep Test (PIST), Sucrose Preference Test (SPT), and Morris Water Maze (MWM). Histopathological and immunofluorescence evaluations of hippocampal tissues were performed. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure neurotransmitter levels (5-Hydroxytryptamine [5-HT], 5-Hydroxytryptophan [5-HTP], Gamma-aminobutyric acid [GABA], glutamate [GLU]) and pro-inflammatory cytokines (Tumor Necrosis Factor Alpha [TNF-α], Interleukin-6 [IL-6], Interleukin-1 beta [IL-1β], Interleukin-8 [IL-8]). In vitro, corticosterone-induced neurotoxicity in HT22 hippocampal cells was assessed, and the role of the Nrf2/HO-1 pathway was examined through molecular docking, gene silencing, and Western blot.</p><p><strong>Results: </strong>Ginsenoside Rg1 treatment significantly improved PCPA-induced insomnia symptoms in a dose-dependent manner, as evidenced by reduced sleep latency, increased sleep duration, restored sucrose preference, and improved spatial memory. Histopathological analysis revealed that Ginsenoside Rg1 mitigated neuronal damage and astrocytic activation. Neurotransmitter imbalances were corrected, and inflammation was alleviated, as reflected by reductions in pro-inflammatory cytokines and increased interleukin-10 (IL-10) levels. Mechanistically, Ginsenoside Rg1 inhibited NLRP3 inflammasome activation, pyroptosis, and reduced IL-1β and IL-8 levels in both in vivo and in vitro models. The activation of the Nrf2/HO-1 pathway was further confirmed by molecular docking, immunofluorescence, and Western blot, demonstrating that Nrf2 activation was critical for the anti-inflammatory effects of Ginsenoside Rg1.</p><p><strong>Conclusion: </strong>Ginsenoside Rg1 effectively alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis, with its neuroprotective effects mediated through the activation of the Nrf2/HO-1 pathway. These findings suggest Ginsenoside Rg1 as a potential therapeutic agent for insomnia and related neuroinflammatory conditions.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-10\",\"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/s00213-025-06828-5\",\"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/s00213-025-06828-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Ginsenoside Rg1 alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis through the Nrf2/HO-1 pathway in mice.
Objectives: This study aims to investigate the neuroprotective effects of Ginsenoside Rg1 in alleviating P-chlorophenylalanine (PCPA)-induced insomnia and explore its underlying mechanisms involving the inhibition of NOD-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation and pyroptosis through the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway in mice.
Methods: Sprague-Dawley rats were randomly divided into five groups: control, sleep deprivation (SD, PCPA-induced insomnia), and three treatment groups receiving different doses of Ginsenoside Rg1 (low, medium, and high). Behavioral assessments included the Pentobarbital Sodium-Induced Sleep Test (PIST), Sucrose Preference Test (SPT), and Morris Water Maze (MWM). Histopathological and immunofluorescence evaluations of hippocampal tissues were performed. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure neurotransmitter levels (5-Hydroxytryptamine [5-HT], 5-Hydroxytryptophan [5-HTP], Gamma-aminobutyric acid [GABA], glutamate [GLU]) and pro-inflammatory cytokines (Tumor Necrosis Factor Alpha [TNF-α], Interleukin-6 [IL-6], Interleukin-1 beta [IL-1β], Interleukin-8 [IL-8]). In vitro, corticosterone-induced neurotoxicity in HT22 hippocampal cells was assessed, and the role of the Nrf2/HO-1 pathway was examined through molecular docking, gene silencing, and Western blot.
Results: Ginsenoside Rg1 treatment significantly improved PCPA-induced insomnia symptoms in a dose-dependent manner, as evidenced by reduced sleep latency, increased sleep duration, restored sucrose preference, and improved spatial memory. Histopathological analysis revealed that Ginsenoside Rg1 mitigated neuronal damage and astrocytic activation. Neurotransmitter imbalances were corrected, and inflammation was alleviated, as reflected by reductions in pro-inflammatory cytokines and increased interleukin-10 (IL-10) levels. Mechanistically, Ginsenoside Rg1 inhibited NLRP3 inflammasome activation, pyroptosis, and reduced IL-1β and IL-8 levels in both in vivo and in vitro models. The activation of the Nrf2/HO-1 pathway was further confirmed by molecular docking, immunofluorescence, and Western blot, demonstrating that Nrf2 activation was critical for the anti-inflammatory effects of Ginsenoside Rg1.
Conclusion: Ginsenoside Rg1 effectively alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis, with its neuroprotective effects mediated through the activation of the Nrf2/HO-1 pathway. These findings suggest Ginsenoside Rg1 as a potential therapeutic agent for insomnia and related neuroinflammatory conditions.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
