{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T05:31:26Z","timestamp":1775453486645,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Basic and Applied Basic Research Fund","award":["2022A1515220101"],"award-info":[{"award-number":["2022A1515220101"]}]},{"name":"Guangdong Provincial Administration of Traditional Chinese Medicine Research Project","award":["20241078"],"award-info":[{"award-number":["20241078"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Aim: This study investigates how Buyang Huanwu Decoction (BHD) protects against cerebral ischemic damage by targeting the NLRP3\/Caspase-1 pathway. Methods: The fingerprint of BHD was analyzed by HPLC-UV. Migratory chemicals in BHD-containing cerebrospinal fluid (BHD-CCSF) were analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). The effects of BHD on the NLRP3\/Caspase-1 pathway, IL-18 and IL-1\u03b2 levels in oxygen and glucose deprivation\/reperfusion (OGD\/R) cells were assessed by Western blot and ELISA. Cerebral infarction severity in permanent middle cerebral artery occlusion (pMCAO) mice was assessed by mNSS scores and staining. Protein and mRNA levels of the NLRP3\/Caspase-1 pathway and inflammatory factors (IL-18, IL-1\u03b2) were measured. Results: BHD-containing serum (BHD-CS), BHD-CCSF, and Calycosin (Cal) reduced NLRP3, Caspase-1, ASC, GSDMD proteins, IL-18 and IL-1\u03b2 in OGD\/R cells. In pMCAO mice, BHD decreased pathway-related proteins and mRNA and inflammatory factors and alleviated brain injury. Conclusions: BHD ameliorates cerebral ischemia by inhibiting the NLRP3\/Caspase-1 pathway, thereby suppressing pyroptosis and inflammation.<\/jats:p>","DOI":"10.3390\/ph19040567","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:51:03Z","timestamp":1775130663000},"page":"567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the Mechanism of Buyang Huanwu Decoction in Treating Ischemic Stroke by Regulating the NLRP3\/Caspase-1 Signaling Pathway"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4587-5073","authenticated-orcid":false,"given":"Keqi","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Nie","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Die","family":"Pei","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieyi","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, University Town, Panyu District, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3892\/ijmm.2021.5070","article-title":"Neuronal Injuries in Cerebral Infarction and Ischemic Stroke: From Mechanisms to Treatment (Review)","volume":"49","author":"Zhao","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics\u20142020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000495041","article-title":"An Appraisal of the 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke","volume":"8","author":"Jadhav","year":"2020","journal-title":"Interv. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in Neurodegenerative Disorders: The Roles of Microglia and Astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rajesh, Y., and Kanneganti, T.-D. (2022). Innate Immune Cell Death in Neuroinflammation and Alzheimer\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11121885"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s11910-023-01282-2","article-title":"Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke","volume":"23","author":"Alsbrook","year":"2023","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_7","first-page":"145","article-title":"Research Progress of Mechanisms and Drug Therapy for Inflammation in Ischemic Stroke","volume":"45","author":"Zhao","year":"2021","journal-title":"Prog. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shen, J., Zhu, Y., Huang, K., Jiang, H., Shi, C., Xiong, X., Zhan, R., and Pan, J. (2016). Buyang Huanwu Decoction Attenuates H2O2-Induced Apoptosis by Inhibiting Reactive Oxygen Species-Mediated Mitochondrial Dysfunction Pathway in Human Umbilical Vein Endothelial Cells. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1152-7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","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_11","unstructured":"L\u00fc, Y. (2020). The NLRP-3\/Caspase-1\/GSDMD Signalling Axis Mediates Pyroptosis in Microglia. [Master\u2019s Thesis, Soochow University]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116599","DOI":"10.1016\/j.lfs.2019.116599","article-title":"Hispidulin Exhibits Neuroprotective Activities against Cerebral Ischemia Reperfusion Injury through Suppressing NLRP3-Mediated Pyroptosis","volume":"232","author":"An","year":"2019","journal-title":"Life Sci."},{"key":"ref_13","first-page":"197","article-title":"Buyang Huanwu Decoction Fraction Protects against Cerebral Ischemia\/Reperfusion Injury by Attenuating the Inflammatory Response and Cellular Apoptosis","volume":"8","author":"Jin","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9937264","DOI":"10.1155\/2021\/9937264","article-title":"Protective Effect of Buyang Huanwu Decoction on Cerebral Ischemia Reperfusion Injury by Alleviating Autophagy in the Ischemic Penumbra","volume":"2021","author":"Zhao","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115953","DOI":"10.1016\/j.jep.2022.115953","article-title":"Buyang Huanwu Decoction Alleviates Oxidative Injury of Cerebral Ischemia-Reperfusion through PKC\u03b5\/Nrf2 Signaling Pathway","volume":"303","author":"Yin","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1159\/000487031","article-title":"Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats","volume":"45","author":"Wang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109488","DOI":"10.1016\/j.abb.2022.109488","article-title":"Calycosin Decreases Cerebral Ischemia\/Reperfusion Injury by Suppressing ACSL4-Dependent Ferroptosis","volume":"734","author":"Liu","year":"2023","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e46966","DOI":"10.1097\/MD.0000000000046966","article-title":"Identification of Diagnostic Biomarkers for Ischemic Stroke and Drug Targets of Buyang Huanwu Decoction: A Bioinformatics and Network Pharmacology Study","volume":"105","author":"Fu","year":"2026","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Qin, Y., Hu, S., Mawen, S., Pan, S., Huai, Y., Liang, G., Chen, T., Zhao, F., Dong, H., and Yao, X. (2025). Neuroprotective Mechanisms of Buyang Huanwu Decoction in Ischemic Stroke. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1620533"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111032","DOI":"10.1016\/j.brainresbull.2024.111032","article-title":"Buyang Huanwu Decoction Suppresses Ischemic Stroke by Suppressing Glycolysis and Cell Apoptosis in Rat Brain Microvascular Endothelial Cells","volume":"215","author":"Song","year":"2024","journal-title":"Brain Res. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120003","DOI":"10.1016\/j.jep.2025.120003","article-title":"Bioactive Equivalent Combinatorial Compounds Contributing to the Holistic Effect of Traditional Chinese Medicine Bupleuri Chinense DC","volume":"350","author":"Zhao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105935","DOI":"10.1016\/j.fitote.2024.105935","article-title":"Investigation of the Underlying Mechanism of Buyang Huanwu Decoction in Ischemic Stroke by Integrating Systems Pharmacology-Proteomics and in Vivo Experiments","volume":"175","author":"Liao","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_23","first-page":"1227","article-title":"A Serum Pharmacochemical Study on the Pharmacodynamic Substances Basis of the Anti-Ischemic Injury of Buyang Huanwu Decoction","volume":"34","author":"Zeng","year":"2023","journal-title":"New Tradit. Chin. Med. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114166","DOI":"10.1016\/j.jpba.2021.114166","article-title":"Metabolomics Analysis of the Therapeutic Effects of Qiwei Tongbi Oral Liquid on Rheumatoid Arthritis in Rats","volume":"202","author":"Tang","year":"2021","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119275","DOI":"10.1016\/j.jep.2024.119275","article-title":"Buyang Huanwu Decoction Prevents Hemorrhagic Transformation after Delayed T-PA Infusion via Inhibiting NLRP3 Inflammasome\/Pyroptosis Associated with Microglial PGC-1\u03b1","volume":"340","author":"Pan","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154845","DOI":"10.1016\/j.phymed.2023.154845","article-title":"Calycosin Alleviates Cerebral Ischemia\/Reperfusion Injury by Repressing Autophagy via STAT3\/FOXO3a Signaling Pathway","volume":"115","author":"Xu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1007\/s11481-019-09903-9","article-title":"Calycosin Preserves BDNF\/TrkB Signaling and Reduces Post-Stroke Neurological Injury after Cerebral Ischemia by Reducing Accumulation of Hypertrophic and TNF-\u03b1-Containing Microglia in Rats","volume":"15","author":"Hsu","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177707","DOI":"10.1016\/j.ejphar.2025.177707","article-title":"Calycosin Regulates Gut Microbiota-Bile Acid-FXR Axis to Protect Rats from Cerebral Ischemia-Reperfusion Injury","volume":"1000","author":"Zhou","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10711","DOI":"10.2147\/JIR.S480262","article-title":"Calycosin Ameliorates Neuroinflammation via TLR4-Mediated Signal Following Cerebral Ischemia\/Reperfusion Injury in Vivo and in Vitro","volume":"17","author":"Yang","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuroscience.2017.04.025","article-title":"Role of Choroid Plexus in Cerebrospinal Fluid Hydrodynamics","volume":"354","author":"Klarica","year":"2017","journal-title":"Neuroscience"},{"key":"ref_31","first-page":"5274","article-title":"Protective Effect of Tongqiao Huoxue Decoction Containing Cerebrospinal Fluid On OGD\/R-Damaged HT22 Cells via Regulation of ASK1\/MKK4\/JNK Signaling Pathway","volume":"47","author":"Yuan","year":"2022","journal-title":"China J. Chin. Mater. Medica"},{"key":"ref_32","first-page":"1174","article-title":"Protective Effect of Drug-Containing Cerebrospinal Fluid of Dandengtongnao Capsule on Cerebral Microvascular Endothelial Cells in Rats Injured by OGD\/R","volume":"40","author":"Gao","year":"2018","journal-title":"Chin. Tradit. Pat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s12906-017-1680-9","article-title":"Buyang Huanwu Decoction Facilitates Neurorehabilitation through an Improvement of Synaptic Plasticity in Cerebral Ischemic Rats","volume":"17","author":"Pan","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1007\/s12035-020-02016-y","article-title":"Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ischemic Stroke: Involvements of EGFR\/PI3K\/Akt\/Bad\/14-3-3 and Jak2\/Stat3\/Cyclin D1 Signaling Cascades","volume":"57","author":"Chen","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and Regulation of NLRP3 Inflammasome Activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5160","DOI":"10.1002\/jcp.26287","article-title":"Inflammasome: Its Role in Traumatic Brain and Spinal Cord Injury","volume":"233","author":"Mortezaee","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.brainresbull.2020.10.009","article-title":"Targeting Pyroptosis to Regulate Ischemic Stroke Injury: Molecular Mechanisms and Preclinical Evidences","volume":"165","author":"Ye","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"136576","DOI":"10.1016\/j.neulet.2022.136576","article-title":"Inhibition of PRMT5 Attenuates Cerebral Ischemia\/Reperfusion\u2013Induced Inflammation and Pyroptosis through Suppression of NF\u2013\u039aB\/NLRP3 Axis","volume":"776","author":"Wu","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116011","DOI":"10.1016\/j.jep.2022.116011","article-title":"Tongxinluo Attenuates Atherosclerosis by Inhibiting ROS\/NLRP3\/Caspase-1-Mediated Endothelial Cell Pyroptosis","volume":"304","author":"Jiang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, K.L., Li, W.H., Liu, Y.J., Wei, Y.J., Ren, Y.K., Mai, C.D., Zhang, S.Y., Zuo, Y., Sun, Z.Z., and Li, D.L. (2022). Hydrogen Sulfide Attenuates Neuroinflammation by Inhibiting the NLRP3\/Caspase-1\/GSDMD Pathway in Retina or Brain Neuron Following Rat Ischemia\/Reperfusion. Brain Sci., 12.","DOI":"10.3390\/brainsci12091245"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112051","DOI":"10.1016\/j.jep.2019.112051","article-title":"Neuroprotective Effect of Glycosides in Buyang Huanwu Decoction on Pyroptosis Following Cerebral Ischemia-Reperfusion Injury in Rats","volume":"242","author":"She","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41590-020-0669-6","article-title":"FDA-Approved Disulfiram Inhibits Pyroptosis by Blocking Gasdermin D Pore Formation","volume":"21","author":"Hu","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1080\/13880209.2022.2102656","article-title":"Combination of Paeoniflorin and Calycosin-7-Glucoside Alleviates Ischaemic Stroke Injury via the PI3K\/AKT Signalling Pathway","volume":"60","author":"Wang","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9925561","DOI":"10.1155\/2021\/9925561","article-title":"Astragaloside IV Alleviates Cerebral Ischemia-Reperfusion Injury through NLRP3 Inflammasome-Mediated Pyroptosis Inhibition via Activating Nrf2","volume":"2021","author":"Xiao","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_45","first-page":"43","article-title":"Protective Effects of Different Doses of Calycosin from Astragalus on Neuronal Cells of Rats with Cerebral Ischemia-Reperfusion Injury","volume":"37","author":"Zhang","year":"2022","journal-title":"J. Hebei Tradit. Chin. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177621","DOI":"10.1016\/j.ejphar.2025.177621","article-title":"Calycosin Treats Acute Myocardial Infarction via NLRP3 Inflammasome: Bioinformatics, Network Pharmacology and Experimental Validation","volume":"997","author":"Yuan","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_47","first-page":"830","article-title":"Simultaneous Content Determination of 10 Components in Lyophilized Product of Buyang Huanwu Decoction on UPLC","volume":"33","author":"Liu","year":"2022","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible Middle Cerebral Artery Occlusion without Craniectomy in Rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:12:15Z","timestamp":1775448735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ph19040567"],"URL":"https:\/\/doi.org\/10.3390\/ph19040567","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}