{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:27:18Z","timestamp":1791919638556,"version":"4.3.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Mitochondrial quality control (MQC) is an important mechanism of neural repair after cerebral ischemia (CI). Recent studies have shown that caveolin-1 (Cav-1) is an important signaling molecule in the process of CI injury, but its mechanism of regulating MQC after CI is still unclear. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine formula that is often used to treat CI. Unfortunately, its mechanism of action is still obscure.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In this study, we tested the hypothesis that BHD can regulate MQC through Cav-1 and exert an anti-cerebral ischemia injury effect. We used Cav-1 knockout mice and their homologous wild-type mice, replicated middle cerebral artery occlusion (MCAO) model and BHD intervention. Neurobehavioral scores and pathological detection were used to evaluate neurological function and neuron damage, transmission electron microscopy and enzymology detection of mitochondrial damage. Finally, western blot and RT-qPCR expression of MQC-related molecules were tested.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> After CI, mice showed neurologic impairment, neuronal damage, and significant destruction of mitochondrial morphology and function, and MQC was imbalanced. Cav-1 deletion aggravated the damage to neurological function, neurons, mitochondrial morphology and mitochondrial function after CI, aggravated the imbalance of mitochondrial dynamics, and inhibited mitophagy and biosynthesis. BHD can maintain MQC homeostasis after CI through Cav-1 and improve CI injury.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Cav-1 can affect CI injury by regulating MQC, and this mechanism may be another target of BHD for anti-cerebral ischemia injury.<\/jats:p>","DOI":"10.3389\/fphar.2023.1137609","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T15:55:23Z","timestamp":1683734123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Buyang Huanwu Decoction alleviates cerebral ischemic injury through modulating caveolin-1-mediated mitochondrial quality control"],"prefix":"10.3389","volume":"14","author":[{"given":"Yaqian","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengming","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1007\/s12035-017-0503-9","article-title":"Mitochondrial quality control and disease: Insights into ischemia-reperfusion injury","volume":"55","author":"Anzell","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.jns.2017.02.043","article-title":"Mitochondrial dysfunction - silent killer in cerebral ischemia","volume":"375","author":"Bakthavachalam","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3389\/fcell.2020.00239","article-title":"MitophAging: Mitophagy in aging and disease","volume":"8","author":"Bakula","year":"2020","journal-title":"Front. Cell. Dev. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.cub.2011.03.030","article-title":"Caveolin-1 deficiency causes cholesterol-dependent mitochondrial dysfunction and apoptotic susceptibility","volume":"21","author":"Bosch","year":"2011","journal-title":"Curr. Biol. CB"},{"key":"B5","doi-asserted-by":"publisher","first-page":"9020169","DOI":"10.3390\/biomedicines9020169","article-title":"Different roles of mitochondria in cell death and inflammation: Focusing on mitochondrial quality control in ischemic stroke and reperfusion","volume":"9","author":"Carinci","year":"2021","journal-title":"Biomedicines"},{"key":"B6","doi-asserted-by":"publisher","first-page":"112445","DOI":"10.1016\/j.biopha.2021.112445","article-title":"Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia","volume":"145","author":"Chen","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","first-page":"67857","DOI":"10.18632\/oncotarget.12346","article-title":"Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction degradation","volume":"7","author":"Choi","year":"2016","journal-title":"Oncotarget"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e13579","DOI":"10.15252\/emmm.202013579","article-title":"High-throughput screening identifies suppressors of mitochondrial fragmentation in OPA1 fibroblasts","volume":"13","author":"Cretin","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1093\/cercor\/bhx196","article-title":"Neuron-targeted caveolin-1 promotes ultrastructural and functional hippocampal synaptic plasticity","volume":"28","author":"Egawa","year":"2018","journal-title":"Cereb. Cortex"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1161\/STROKEAHA.111.642710","article-title":"Angiogenesis: A harmonized target for recovery after stroke","volume":"43","author":"Ergul","year":"2012","journal-title":"Stroke"},{"key":"B12","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/s0022-5223(19)37950-4","article-title":"Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man","volume":"79","author":"Flameng","year":"1980","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1152\/physrev.00011.2017","article-title":"Neuronal cell death","volume":"98","author":"Fricker","year":"2018","journal-title":"Physiol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1111\/j.1471-4159.2004.02917.x","article-title":"A role for caveolin-1 in post-injury reactive neuronal plasticity","volume":"92","author":"Gaudreault","year":"2005","journal-title":"J. Neurochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, regional, and national burden of neurological disorders, 1990-2016: A systematic analysis for the global burden of disease study 2016","volume":"18","year":"2019","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.lfs.2016.09.021","article-title":"Disrupted mitochondrial genes and inflammation following stroke","volume":"166","author":"Gibbs","year":"2016","journal-title":"Life Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4103\/1673-5374.264442","article-title":"Angiogenesis and neuronal remodeling after ischemic stroke","volume":"15","author":"Hatakeyama","year":"2020","journal-title":"Neural Regen. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/cells8080897","article-title":"Parkin-Dependent mitophagy is required for the inhibition of ATF4 on NLRP3 inflammasome activation in cerebral ischemia-reperfusion injury in rats","volume":"8","author":"He","year":"2019","journal-title":"Cells"},{"key":"B19","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1186\/s12974-018-1387-y","article-title":"A review of the role of cav-1 in neuropathology and neural recovery after ischemic stroke","volume":"15","author":"Huang","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"B20","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3969\/j.issn.1008-9691.2016.06.020","article-title":"Effect of Buyang Huanwu Decoction on the expression of inflammatory factors after cerebral ischemia in caveolin-1 knockout mice","volume":"23","author":"Huang","year":"2016","journal-title":"Chin. J. Integr. Traditional West. Med. Intensive Crit. Care"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e20534","DOI":"10.1097\/MD.0000000000020534","article-title":"Effects and safety of buyang-huanwu decoction for the treatment of patients with acute ischemic stroke: A protocol of systematic review and meta-analysis","volume":"99","author":"Jiang","year":"2020","journal-title":"Med. Baltim."},{"key":"B22","doi-asserted-by":"publisher","first-page":"174324","DOI":"10.1016\/j.ejphar.2021.174324","article-title":"Caveolin-1 attenuates acetaminophen aggravated lipid accumulation in alcoholic fatty liver by activating mitophagy via the Pink-1\/Parkin pathway","volume":"908","author":"Jiang","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"102304","DOI":"10.1016\/j.redox.2022.102304","article-title":"Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy","volume":"52","author":"Jiang","year":"2022","journal-title":"Redox Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4558","DOI":"10.3390\/ijms22094558","article-title":"Role of PGC-1\u03b1 in the mitochondrial NAD+ pool in metabolic diseases","volume":"22","author":"Koh","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1161\/01.str.25.9.1794","article-title":"Role of angiogenesis in patients with cerebral ischemic stroke","volume":"25","author":"Krupinski","year":"1994","journal-title":"Stroke"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1042\/BST20210272","article-title":"The dynamics of mitochondrial autophagy at the initiation stage","volume":"49","author":"Ktistakis","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1089\/neu.2008.0746","article-title":"CD38 facilitates recovery from traumatic brain injury","volume":"26","author":"Levy","year":"2009","journal-title":"J. Neurotrauma"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1242\/jcs.114.7.1397","article-title":"Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria","volume":"114","author":"Li","year":"2001","journal-title":"J. Cell Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"755665","DOI":"10.3389\/fnagi.2021.755665","article-title":"Exercise-induced benefits for alzheimer's disease by stimulating mitophagy and improving mitochondrial function","volume":"13","author":"Liang","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B30","first-page":"22","article-title":"Effects of Buyang Huanwu Decoction on caveolin1 and 2 in focal cerebral ischemia rats","volume":"28","author":"Liu","year":"2008","journal-title":"J. Hunan Univ. traditional Chin. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1089\/neu.2016.4764","article-title":"Extracellular signal-regulated kinase\/nuclear factor-erythroid2-like2\/heme oxygenase-1 pathway-mediated mitophagy alleviates traumatic brain injury-induced intestinal mucosa damage and epithelial barrier dysfunction","volume":"34","author":"Liu","year":"2017","journal-title":"J. Neurotrauma"},{"key":"B32","doi-asserted-by":"publisher","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"},{"key":"B33","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.biopsych.2015.09.020","article-title":"Neuron-targeted caveolin-1 improves molecular signaling, plasticity, and behavior dependent on the Hippocampus in adult and aged mice","volume":"81","author":"Mandyam","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.tox.2017.07.019","article-title":"Mitochondrial fusion, fission, and mitochondrial toxicity","volume":"391","author":"Meyer","year":"2017","journal-title":"Toxicology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.4161\/cc.9.11.11848","article-title":"Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the \"reverse warburg effect\": A transcriptional informatics analysis with validation","volume":"9","author":"Pavlides","year":"2010","journal-title":"Cell Cycle"},{"key":"B36","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/acel.12270","article-title":"Caveolae control the anti-inflammatory phenotype of senescent endothelial cells","volume":"14","author":"Powter","year":"2015","journal-title":"Aging Cell"},{"key":"B37","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1152\/physrev.00025.2007","article-title":"Transcriptional paradigms in mammalian mitochondrial biogenesis and function","volume":"88","author":"Scarpulla","year":"2008","journal-title":"Physiol. Rev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cmet.2018.01.011","article-title":"Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics","volume":"27","author":"Schmitt","year":"2018","journal-title":"Cell Metab."},{"key":"B39","doi-asserted-by":"publisher","first-page":"154312","DOI":"10.1016\/j.phymed.2022.154312","article-title":"An evidence-based evaluation of Buyang Huanwu decoction for the treatment of the sequelae of stroke: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials","volume":"104","author":"Shao","year":"2022","journal-title":"Phytomedicine"},{"key":"B40","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/jcsm.12250","article-title":"Trimetazidine restores the positive adaptation to exercise training by mitigating statin-induced skeletal muscle injury","volume":"9","author":"Song","year":"2018","journal-title":"J. Cachexia, Sarcopenia Muscle"},{"key":"B41","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cmet.2014.12.011","article-title":"Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts","volume":"21","author":"Song","year":"2015","journal-title":"Cell Metab."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1007\/s12035-022-02795-6","article-title":"Mitochondrial quality and quantity control: Mitophagy is a potential therapeutic target for ischemic stroke","volume":"59","author":"Song","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"873096","DOI":"10.3389\/fcimb.2022.873096","article-title":"Therapeutic effect of Buyang Huanwu decoction on the gut microbiota and hippocampal metabolism in a rat model of cerebral ischemia","volume":"12","author":"Tang","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2174\/1570161116666180206112215","article-title":"Caveolin-1 in stroke neuropathology and neuroprotection: A novel molecular therapeutic target for ischemic-related injury","volume":"17","author":"Wang","year":"2019","journal-title":"Curr. Vasc. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1007\/s10620-018-5227-9","article-title":"Plasma mtDNA analysis aids in predicting pancreatic necrosis in acute pancreatitis patients: A pilot study","volume":"63","author":"Wu","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"106307","DOI":"10.1016\/j.biocel.2022.106307","article-title":"Caveolin-1 signaling-driven mitochondrial fission and cytoskeleton remodeling promotes breast cancer migration","volume":"152","author":"Xiao","year":"2022","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"786099","DOI":"10.3389\/fnmol.2021.786099","article-title":"Mitochondrial quality control: A pathophysiological mechanism and therapeutic target for stroke","volume":"14","author":"Yang","year":"2021","journal-title":"Front. Molec. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"112866","DOI":"10.1016\/j.yexcr.2021.112866","article-title":"Alleviation of CCCP-induced mitochondrial injury by augmenter of liver regeneration via the PINK1\/Parkin pathway-dependent mitophagy","volume":"409","author":"Zhang","year":"2021","journal-title":"Exp. Cell Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1083\/jcb.201804101","article-title":"Somatic autophagy of axonal mitochondria in ischemic neurons","volume":"218","author":"Zheng","year":"2019","journal-title":"J. Cell Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1007\/s11064-019-02951-w","article-title":"lncRNA ANRIL ameliorates oxygen and glucose deprivation (OGD) induced injury in neuron cells via miR-199a-5p\/CAV-1 Axis","volume":"45","author":"Zhong","year":"2020","journal-title":"Neurochem. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"804","DOI":"10.19378\/j.issn.1003-9783.2016.06.013","article-title":"Effect of Buyang Huanwu decoction on NSCs proliferation in Hippocampus of mice after cerebral ischemia through cav1\/notch1\/hes1 pathway","volume":"27","author":"Zhou","year":"2016","journal-title":"Traditional Chin. Drug Res. Clin. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s13024-018-0295-z","article-title":"GSK3\u03b2-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions","volume":"13","author":"Zhu","year":"2018","journal-title":"Mol. Neurodegener."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1137609\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T15:55:44Z","timestamp":1683734144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1137609\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":52,"alternative-id":["10.3389\/fphar.2023.1137609"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1137609","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"article-number":"1137609"}}