{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:59:30Z","timestamp":1785495570636,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["BUCM-2021-JS-KF-045"],"award-info":[{"award-number":["BUCM-2021-JS-KF-045"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BUCM-2021-JS-KF-045"],"award-info":[{"award-number":["BUCM-2021-JS-KF-045"]}],"id":[{"id":"https:\/\/ror.org\/05damtm70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Insomnia is associated with disrupted sleep architecture, hippocampal pathological alterations, neurotransmitter imbalance, and neuroinflammatory responses. This study evaluated the effects of the Prunella vulgaris compound (PVC) on sleep architecture and hippocampal alterations in p-chlorophenylalanine (PCPA)-induced insomnia model mice and examined their association with NLRP3-related pyroptotic signaling. PVC was characterized using UPLC-Q-Exactive Orbitrap MS and targeted HPLC quantification. PCPA-induced insomnia models were established in ICR and C57BL\/6N mice for pharmacodynamic and molecular assessments and EEG\/EMG recording, respectively. Sleep outcomes were assessed using the pentobarbital-induced sleep test and EEG\/EMG; hippocampal histomorphology, neurotransmitters, and inflammasome- and pyroptosis-related markers were evaluated using histological, biochemical, RT-qPCR, and Western blot analyses. UPLC-MS tentatively characterized 198 constituents, and salviaflaside, rosmarinic acid, and linarin were quantified by HPLC. PVC shortened sleep latency, prolonged sleep duration, reduced wakefulness, increased NREM and REM sleep, and improved sleep continuity. It also attenuated hippocampal histomorphological alterations; modulated 5-HT, GABA, glutamate, and dopamine levels; and reduced NLRP3 inflammasome- and pyroptosis-related markers together with IL-1\u03b2 and IL-18. PVC improved insomnia-like phenotypes and attenuated hippocampal pathological alterations in PCPA-induced insomnia model mice. These effects were associated with improved sleep architecture and neurotransmitter homeostasis and with reduced NLRP3\/caspase-1\/GSDMD-related signaling.<\/jats:p>","DOI":"10.3390\/life16081268","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:11:38Z","timestamp":1785492698000},"page":"1268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prunella vulgaris Compound Improves Sleep Architecture and Attenuates Hippocampal Injury in Insomnia Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Kai","family":"Wang","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojia","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijin","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fafeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102446, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.pcad.2023.02.005","article-title":"Sleep physiology, pathophysiology, and sleep hygiene","volume":"77","author":"Baranwal","year":"2023","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00281-021-00904-6","article-title":"The contribution of sleep to the neuroendocrine regulation of rhythms in human leukocyte traffic","volume":"44","author":"Lange","year":"2022","journal-title":"Semin Immunopathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1038\/s41467-022-30712-x","article-title":"The gut microbiota-bile acid axis links the positive association between chronic insomnia and cardiometabolic diseases","volume":"13","author":"Jiang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70089","DOI":"10.1111\/jsr.70089","article-title":"The Prevalence of Insomnia Disorder in the General Population: A Meta-Analysis","volume":"34","author":"Weinreich","year":"2025","journal-title":"J. Sleep Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102121","DOI":"10.1016\/j.smrv.2025.102121","article-title":"Estimation of the global prevalence and burden of insomnia: A systematic literature review-based analysis","volume":"82","author":"Benjafield","year":"2025","journal-title":"Sleep Med. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e252493","DOI":"10.1001\/jamanetworkopen.2025.2493","article-title":"Electronic Screen Use and Sleep Duration and Timing in Adults","volume":"8","author":"Zhong","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.sleep.2024.10.021","article-title":"The association between insomnia and cognitive decline: A scoping review","volume":"124","author":"Zhang","year":"2024","journal-title":"Sleep Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.neuron.2023.03.005","article-title":"Sleep-A brain-state serving systems memory consolidation","volume":"111","author":"Brodt","year":"2023","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.tins.2023.08.003","article-title":"The role of the hippocampus in the consolidation of emotional memories during sleep","volume":"46","author":"Pronier","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e14134","DOI":"10.1111\/jsr.14134","article-title":"Crosstalk between the subiculum and sleep-wake regulation: A review","volume":"33","author":"Rahimi","year":"2024","journal-title":"J. Sleep Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e14252","DOI":"10.1111\/jsr.14252","article-title":"Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?","volume":"34","author":"Riemann","year":"2025","journal-title":"J. Sleep Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115419","DOI":"10.1016\/j.expneurol.2025.115419","article-title":"Sleep deprivation-induced cognitive impairment: Unraveling the role of neuroinflammation","volume":"394","author":"Yuan","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113400","DOI":"10.1016\/j.bbr.2021.113400","article-title":"Chronic sleep deprivation exacerbates cognitive and synaptic plasticity impairments in APP\/PS1 transgenic mice","volume":"412","author":"Wang","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e11609","DOI":"10.7717\/peerj.11609","article-title":"NLRP3 inflammasome activation mediates sleep deprivation-induced pyroptosis in mice","volume":"9","author":"Fan","year":"2021","journal-title":"PeerJ"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Amini, M., Yousefi, Z., Ghafori, S.S., and Hassanzadeh, G. (2022). Sleep deprivation and NLRP3 inflammasome: Is there a causal relationship?. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.1018628"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1007\/s00011-023-01790-4","article-title":"Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases","volume":"72","author":"Han","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dai, Z., Liu, W.-C., Chen, X.-Y., Wang, X., Li, J.-L., and Zhang, X. (2023). Gasdermin D-mediated pyroptosis: Mechanisms, diseases, and inhibitors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1178662"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40035-023-00381-x","article-title":"NLRP3 inflammasome in cognitive impairment and pharmacological properties of its inhibitors","volume":"12","author":"Xu","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiong, X., Zuo, Y., Cheng, L., Yin, Z., Hu, T., Guo, M., Han, Z., Ge, X., Li, W., and Wang, Y. (2022). Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.816752"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e14035","DOI":"10.1111\/jsr.14035","article-title":"The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023","volume":"32","author":"Riemann","year":"2023","journal-title":"J. Sleep Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.2174\/1871527320666210618103344","article-title":"Benzodiazepines and sleep architecture: A systematic review","volume":"22","author":"Souza","year":"2023","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s40265-023-01859-8","article-title":"The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials","volume":"83","author":"Pan","year":"2023","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117601","DOI":"10.1016\/j.jep.2023.117601","article-title":"Traditional Chinese medicine for insomnia: Recommendation mapping of the global clinical guidelines","volume":"322","author":"Ye","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","first-page":"483","article-title":"Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: A systematic review","volume":"21","author":"Wang","year":"2023","journal-title":"Chin. J. Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114373","DOI":"10.1016\/j.jep.2021.114373","article-title":"Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS\/MS analysis","volume":"279","author":"Lin","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s10068-024-01663-4","article-title":"Improvement of sleep disorders through the adenosine A receptor agonist effect of Phlomoides umbrosa Turczaninow root extract in pentobarbital-induced ICR mice","volume":"34","author":"Oh","year":"2025","journal-title":"Food Sci. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9359","DOI":"10.1039\/D5FO02926K","article-title":"Sleep-promoting effects and mechanisms of Bacillus coagulans IDCC 1201: Evidence from pentobarbital-induced sleep and electroencephalography analysis in mice","volume":"16","author":"Kim","year":"2025","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126409","DOI":"10.1016\/j.micres.2020.126409","article-title":"Beneficial effect of GABA-rich fermented milk on insomnia involving regulation of gut microbiota","volume":"233","author":"Yu","year":"2020","journal-title":"Microbiol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1055\/a-2360-9639","article-title":"Extracts of Prunella vulgaris Enhanced Pentobarbital-Induced Sleeping Behavior in Mice Potentially via Adenosine A2A Receptor Activity","volume":"90","author":"Sayson","year":"2024","journal-title":"Planta Med."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1268\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:19:07Z","timestamp":1785493147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081268"],"URL":"https:\/\/doi.org\/10.3390\/life16081268","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}