{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:31:21Z","timestamp":1791966681853,"version":"4.3.4"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY19H170001"],"award-info":[{"award-number":["LY19H170001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Spinal cord injury (SCI) often results in abnormal sensory and motor functions. Current interventions for SCI in the clinical setting are not effective partly due to the complexity concerning its pathophysiological mechanism. In the wake of SCI, considerable inflammatory cells assemble around the injured area that induces a series of inflammatory reactions and aggravates tissue lesions, thereby affecting the recovery of the damaged nerve tissue. Therefore, the inhibition of inflammatory responses can improve the repair of the injured spinal cord tissue. Safflower Yellow (SY) is the main active ingredient of Carthamus tinctorius. SY has anti-inflammatory effect, as it can inhibit I\u03baB\u03b1 phosphorylation to impede the NF-\u03baB signaling pathway and p53 nuclear translocation. Besides, SY can limit the release of pro-inflammatory factors, which in turn may alleviate secondary SCI and prevent further complications. In this report, we analyze the pathophysiological mechanism of SCI, the role of inflammatory responses, and how SY interferes with the HMGB1-TLR-4-NF-\u03baB signaling pathway to attenuate inflammatory responses in SCI.<\/jats:p>","DOI":"10.3389\/fnins.2021.803885","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T04:37:23Z","timestamp":1640320643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["The Repression of the HMGB1-TLR4-NF-\u03baB Signaling Pathway by Safflower Yellow May Improve Spinal Cord Injury"],"prefix":"10.3389","volume":"15","author":[{"given":"Lu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson O. A.","family":"Botchway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"914","DOI":"10.5966\/sctm.2015-0381","article-title":"concise review: bridging the gap: novel neuroregenerative and neuroprotective strategies in spinal cord injury.","volume":"5","author":"Ahuja","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1093\/neuros\/nyw080","article-title":"Traumatic spinal cord injury-repair and regeneration.","volume":"80","author":"Ahuja","year":"2017","journal-title":"Neurosurgery"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00027","article-title":"Biomarkers in spinal cord injury: prognostic insights and future potentials.","volume":"10","author":"Albayar","year":"2019","journal-title":"Front. Neurol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00282","article-title":"Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms.","volume":"10","author":"Alizadeh","year":"2019","journal-title":"Front. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1111\/adb.12365","article-title":"Oleoylethanolamide prevents neuroimmune HMGB1\/TLR4\/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration.","volume":"22","author":"Ant\u00f3n","year":"2017","journal-title":"Addict. Biol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00098","article-title":"Inflammogenesis of secondary spinal cord injury.","volume":"10","author":"Anwar","year":"2016","journal-title":"Front. Cell Neurosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11655-013-1354-5","article-title":"Phytochemistry, pharmacology and medicinal properties of Carthamus tinctorius L.","volume":"19","author":"Asgarpanah","year":"2013","journal-title":"Chin. J. Integr. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1097\/00019052-200206000-00021","article-title":"Targeting the host inflammatory response in traumatic spinal cord injury.","volume":"15","author":"Bethea","year":"2002","journal-title":"Curr. Opin. Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.3892\/ijmm.2020.4509","article-title":"A novel CX3CR1 inhibitor AZD8797 facilitates early recovery of rat acute spinal cord injury by inhibiting inflammation and apoptosis.","volume":"45","author":"Chen","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1193-6","article-title":"Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-\u03baB pathway dependent of HDAC3.","volume":"15","author":"Chen","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6672","DOI":"10.19082\/6672","article-title":"Medical uses of Carthamus tinctorius L. (Safflower): a comprehensive review from traditional medicine to modern medicine.","volume":"10","author":"Delshad","year":"2018","journal-title":"Electron. Phys."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020744","article-title":"Systemic inflammation and the breakdown of intestinal homeostasis are key events in chronic spinal cord injury patients.","volume":"22","author":"Diaz","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/jnc.13607","article-title":"Neuroinflammation: the devil is in the details.","author":"DiSabato","year":"2016","journal-title":"J. Neurochem."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7219740","article-title":"Safflower yellow B protects brain against cerebral ischemia reperfusion injury through AMPK\/NF-kB pathway.","volume":"2019","author":"Du","year":"2019","journal-title":"Evid. Based Compl. Alternat. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1089\/neu.2020.7378","article-title":"Intensive locomotor training provides sustained alleviation of chronic spinal cord injury-associated neuropathic pain: a two-year pre-clinical study.","volume":"38","author":"Dugan","year":"2021","journal-title":"J. Neurotrauma"},{"key":"B16","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1177\/0963689718755778","article-title":"Microenvironment imbalance of spinal cord injury.","volume":"27","author":"Fan","year":"2018","journal-title":"Cell Transplant."},{"key":"B17","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1007\/s12264-013-1354-7","article-title":"Protective effects of batroxobin on spinal cord injury in rats.","volume":"29","author":"Fan","year":"2013","journal-title":"Neurosci. Bull."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01973-4","article-title":"Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages\/microglia polarization and affords neuroprotection after spinal cord injury.","volume":"17","author":"Fan","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.cell.2020.03.054","article-title":"Restoring the sense of touch using a sensorimotor demultiplexing neural interface.","volume":"181","author":"Ganzer","year":"2020","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00333-8","article-title":"Parthenolide promotes the repair of spinal cord injury by modulating M1\/M2 polarization via the NF-\u03baB and STAT 1\/3 signaling pathway.","volume":"6","author":"Gaojian","year":"2020","journal-title":"Cell Death Discov."},{"key":"B21","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s13311-018-0630-7","article-title":"Glial cells shape pathology and repair after spinal cord injury.","volume":"15","author":"Gaudet","year":"2018","journal-title":"Neurotherapeutics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3956","DOI":"10.1523\/JNEUROSCI.3992-08.2009","article-title":"Macrophages promote axon regeneration with concurrent neurotoxicity.","volume":"29","author":"Gensel","year":"2009","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s11011-019-00528-8","article-title":"Protective effect of oxymatrine against acute spinal cord injury in rats via modulating oxidative stress, inflammation and apoptosis.","volume":"35","author":"Guan","year":"2020","journal-title":"Metab. Brain Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1080\/10790268.2017.1329076","article-title":"Assessment and management of acute spinal cord injury: from point of injury to rehabilitation.","volume":"40","author":"Hachem","year":"2017","journal-title":"J. Spinal Cord Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/nm.4354","article-title":"Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury.","volume":"23","author":"Hara","year":"2017","journal-title":"Nat. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1179\/2045772315Y.0000000045","article-title":"Cross-sectional associations of pulmonary function with systemic inflammation and oxidative stress in individuals with chronic spinal cord injury.","volume":"39","author":"Hart","year":"2016","journal-title":"J. Spinal Cord Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/sj.sc.3101483","article-title":"Post-traumatic inflammation following spinal cord injury.","volume":"41","author":"Hausmann","year":"2003","journal-title":"Spinal Cord"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1089\/neu.2017.5519","article-title":"Persons with chronic spinal cord injury have decreased natural killer cell and increased toll-like receptor\/inflammatory gene expression.","volume":"35","author":"Herman","year":"2018","journal-title":"J. Neurotrauma"},{"key":"B29","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41556-018-0039-x","article-title":"Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons.","volume":"20","author":"Hervera","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41593-018-0099-z","article-title":"A brainstem bypass for spinal cord injury.","volume":"21","author":"Hilton","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/bs.vh.2016.11.007","article-title":"Neurotrophic Factors used to treat spinal cord injury.","volume":"104","author":"Hodgetts","year":"2017","journal-title":"Vitam. Horm."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00363","article-title":"Electroacupuncture suppresses the NF-\u03baB signaling pathway by upregulating cylindromatosis to alleviate inflammatory injury in cerebral ischemia\/reperfusion rats.","volume":"10","author":"Jiang","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"189","DOI":"10.14348\/molcells.2014.2353","article-title":"NF-\u03baB in cellular senescence and cancer treatment.","volume":"37","author":"Jing","year":"2014","journal-title":"Mol. Cells"},{"key":"B34","first-page":"1141","article-title":"Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1\/TLR4\/NF-\u03baB signaling pathway.","volume":"8","author":"Kang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1394-7","article-title":"Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-\u03baB pathway inhibition.","volume":"16","author":"Karova","year":"2019","journal-title":"J Neuroinflammation."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.5114\/aoms.2017.65650","article-title":"Comparative effects of methylprednisolone and tetracosactide (ACTH1-24) on ischemia\/reperfusion injury of the rabbit spinal cord.","volume":"14","author":"Kertmen","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"13435","DOI":"10.1523\/JNEUROSCI.3257-09.2009","article-title":"Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord.","volume":"29","author":"Kigerl","year":"2009","journal-title":"J. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1002\/jnr.24114","article-title":"Myelin as an inflammatory mediator: myelin interactions with complement, macrophages, and microglia in spinal cord injury.","volume":"96","author":"Kopper","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.spinee.2003.07.007","article-title":"Pathophysiology and pharmacologic treatment of acute spinal cord injury.","volume":"4","author":"Kwon","year":"2004","journal-title":"Spine J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1177\/2192568220901689","article-title":"Nonsteroidal anti-inflammatory drugs and their neuroprotective role after an acute spinal cord injury: a systematic review of animal models.","volume":"11","author":"Lambrechts","year":"2021","journal-title":"Glob. Spine J."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520905425","article-title":"Role of the Hippo signaling pathway in safflower yellow pigment treatment of paraquat-induced pulmonary fibrosis.","volume":"48","author":"Li","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.neulet.2012.12.056","article-title":"Hydroxysafflor yellow a suppresses inflammatory responses of BV2 microglia after oxygen-glucose deprivation.","volume":"535","author":"Li","year":"2013","journal-title":"Neurosci. Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.cyto.2014.12.010","article-title":"Heparin inhibits the inflammatory response induced by LPS and HMGB1 by blocking the binding of HMGB1 to the surface of macrophages.","volume":"72","author":"Li","year":"2015","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01942-x","article-title":"Deficiency of the microglial Hv1 proton channel attenuates neuronal pyroptosis and inhibits inflammatory reaction after spinal cord injury.","volume":"17","author":"Li","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3948795","article-title":"Effects of safflower yellow on the treatment of severe sepsis and septic shock: a randomized controlled clinical trial.","volume":"2016","author":"Li","year":"2016","journal-title":"Evid Based Compl. Alternat. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive astrocytes: production, function, and therapeutic potential.","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia.","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.583611","article-title":"Neuroprotective effect of ketone metabolism on inhibiting inflammatory response by regulating macrophage polarization after acute cervical spinal cord injury in rats.","volume":"14","author":"Lin","year":"2020","journal-title":"Front. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41582-020-0311-0","article-title":"Multi-target approaches to CNS repair: olfactory mucosa-derived cells and heparan sulfates.","volume":"16","author":"Lindsay","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1254\/jphs.14055fp","article-title":"Safflower yellow inhibits angiotensin II-induced adventitial fibroblast proliferation and migration.","volume":"126","author":"Liu","year":"2014","journal-title":"J. Pharmacol. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1097\/FJC.0000000000000710","article-title":"Carthamin yellow protects the heart against ischemia\/reperfusion injury with reduced reactive oxygen species release and inflammatory response.","volume":"74","author":"Lu","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.canlet.2016.02.005","article-title":"Macrophage migration inhibitory factor promotes breast cancer metastasis via activation of HMGB1\/TLR4\/NF kappa B axis.","volume":"375","author":"Lv","year":"2016","journal-title":"Cancer Lett."},{"key":"B53","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1080\/10790268.2016.1142137","article-title":"Effect of acute intermittent hypoxia on motor function in individuals with chronic spinal cord injury following ibuprofen pretreatment: a pilot study.","volume":"40","author":"Lynch","year":"2017","journal-title":"J. Spinal Cord Med."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00378","article-title":"Crosstalk between Wnt\/\u03b2-Catenin and NF-\u03baB signaling pathway during Inflammation.","volume":"7","author":"Ma","year":"2016","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s00401-019-01992-3","article-title":"The origin, fate, and contribution of macrophages to spinal cord injury pathology.","volume":"137","author":"Milich","year":"2019","journal-title":"Acta Neuropathol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12026-015-8698-1","article-title":"Circulating T cell subsets are altered in individuals with chronic spinal cord injury.","volume":"63","author":"Monahan","year":"2015","journal-title":"Immunol. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jconrel.2017.11.044","article-title":"Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury.","volume":"270","author":"Nukolova","year":"2018","journal-title":"J. Control Release"},{"key":"B58","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.neures.2017.10.004","article-title":"Astrocyte reactivity and astrogliosis after spinal cord injury.","volume":"126","author":"Okada","year":"2018","journal-title":"Neurosci. Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s13311-018-0631-6","article-title":"Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses.","volume":"15","author":"Orr","year":"2018","journal-title":"Neurotherapeutics"},{"key":"B60","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s12017-020-08591-6","article-title":"Safflower yellow improves synaptic plasticity in APP\/PS1 mice by regulating microglia activation phenotypes and BDNF\/TrkB\/ERK signaling pathway.","volume":"22","author":"Pang","year":"2020","journal-title":"Neuromol. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"7370","DOI":"10.1074\/jbc.M306793200","article-title":"Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein.","volume":"279","author":"Park","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081841","article-title":"Acute spinal cord injury: a systematic review investigating miRNA families involved.","volume":"20","author":"Pinchi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104788","article-title":"Enolase inhibition alters metabolic hormones and inflammatory factors to promote neuroprotection in spinal cord injury.","volume":"139","author":"Polcyn","year":"2020","journal-title":"Neurochem. Int."},{"key":"B64","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1038\/nn.4338","article-title":"A polarizing question: do M1 and M2 microglia exist?","volume":"19","author":"Ransohoff","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1097\/01.jnen.0000248552.07338.7f","article-title":"Characterization of the early neuroinflammation after spinal cord injury in mice.","volume":"66","author":"Rice","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-016-0331-2","article-title":"Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury.","volume":"18","author":"Rodr\u00edguez-Barrera","year":"2017","journal-title":"BMC Neurosci."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nature00858","article-title":"Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;","volume":"467","author":"Scaffidi","year":"2010","journal-title":"Erratum Nat."},{"key":"B68","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/s41593-019-0385-4","article-title":"Bassoon proteinopathy drives neurodegeneration in multiple sclerosis.","volume":"22","author":"Schattling","year":"2019","journal-title":"Nat. Neurosci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.biopha.2017.12.099","article-title":"Effects of safflower yellow on beta-amyloid deposition and activation of astrocytes in the brain of APP\/PS1 transgenic mice.","volume":"98","author":"Shi","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3892\/mmr.2014.2336","article-title":"Inhibitory effects of hydroxysafflor yellow A on PDGF-BB-induced proliferation and migration of vascular smooth muscle cells via mediating Akt signaling.","volume":"10","author":"Song","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B71","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1097\/MCC.0b013e32835a0e54","article-title":"Management strategies for acute spinal cord injury: current options and future perspectives.","volume":"18","author":"Stahel","year":"2012","journal-title":"Curr. Opin. Crit. Care"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1002\/jnr.21659","article-title":"Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry.","volume":"86","author":"Stirling","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.neulet.2018.10.059","article-title":"Effect of hyperbaric oxygen therapy on HMGB1\/NF-\u03baB expression and prognosis of acute spinal cord injury: a randomized clinical trial.","volume":"692","author":"Sun","year":"2019","journal-title":"Neurosci. Lett."},{"key":"B74","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.1016\/j.bmcl.2010.05.076","article-title":"Hydroxysafflor yellow a suppresses thrombin generation and inflammatory responses following focal cerebral ischemia-reperfusion in rats.","volume":"20","author":"Sun","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/j.biopha.2018.06.119","article-title":"Safflower yellow promotes angiogenesis through p-VHL\/HIF-1\u03b1\/VEGF signaling pathway in the process of osteogenic differentiation.","volume":"107","author":"Tang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B76","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1152\/physrev.00017.2017","article-title":"The biology of regeneration failure and success after spinal cord injury.","volume":"98","author":"Tran","year":"2018","journal-title":"Physiol. Rev."},{"key":"B77","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/SHK.0b013e318186262d","article-title":"Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo.","volume":"31","author":"van Zoelen","year":"2009","journal-title":"Shock"},{"key":"B78","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1021\/acsnano.9b05579","article-title":"Selective modulation of A1 Astrocytes by drug-loaded nano-structured gel in spinal cord injury.","volume":"14","author":"Vismara","year":"2020","journal-title":"ACS Nano"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153305","article-title":"Safflower yellow alleviates osteoarthritis and prevents inflammation by inhibiting PGE2 release and regulating NF-\u03baB\/SIRT1\/AMPK signaling pathways.","volume":"78","author":"Wang","year":"2020","journal-title":"Phytomedicine"},{"key":"B80","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.taap.2013.08.018","article-title":"Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2\/p22(phox) expression.","volume":"273","author":"Wang","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1248\/bpb.34.511","article-title":"Inhibitory effect of safflor yellow on pulmonary fibrosis.","volume":"34","author":"Wang","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"B82","first-page":"E615","article-title":"Tanshinone IIA attenuates chronic pancreatitis-induced pain in rats via downregulation of HMGB1 and TRL4 expression in the spinal cord.","volume":"18","author":"Wang","year":"2015","journal-title":"Pain Phys."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1007\/s10753-019-01024-y","article-title":"Cellular inflammatory response of the spleen after acute spinal cord injury in rat.","volume":"42","author":"Wu","year":"2019","journal-title":"Inflammation"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18265-3","article-title":"Microenvironment-responsive immunoregulatory electrospun fibers for promoting nerve function recovery. Nat Commun. 2020;","volume":"12","author":"Xi","year":"2021","journal-title":"Erratum Nat. Commun."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146495","article-title":"Neuroinflammation induced by secretion of acetylated HMGB1 from activated microglia in hippocampi of mice following chronic cold exposure.","volume":"1726","author":"Xu","year":"2020","journal-title":"Brain Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1111\/jdi.13285","article-title":"Safflower yellow improves insulin sensitivity in high-fat diet-induced obese mice by promoting peroxisome proliferator-activated receptor-\u03b32 expression in subcutaneous adipose tissue.","volume":"11","author":"Yan","year":"2020","journal-title":"J. Diabetes Investig."},{"key":"B87","first-page":"5295","article-title":"Hydroxysafflor yellow A inhibits lipopolysaccharide-induced proliferation and migration of vascular smooth muscle cells via Toll-like receptor-4 pathway.","volume":"8","author":"Yang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1177\/0394632015617065","article-title":"Safflower yellow regulates microglial polarization and inhibits inflammatory response in LPS-stimulated Bv2 cells.","volume":"29","author":"Yang","year":"2016","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"E754","DOI":"10.1152\/ajpendo.00240.2015","article-title":"Heightened TWEAK-NF-\u03baB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.","volume":"310","author":"Yarar-Fisher","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02059-x","article-title":"Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin\/\u03b21 integrin pathway.","volume":"18","author":"Yoshizaki","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.21037\/apm-20-396","article-title":"Role of MK2 signaling pathway mediating microglia\/macrophages polarization in chronic compression injury of cervical spinal cord.","volume":"10","author":"Yu","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"B92","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.brainres.2019.04.007","article-title":"High mobility group box-1 (HMGB1) antagonist BoxA suppresses status epilepticus-induced neuroinflammatory responses associated with Toll-like receptor 2\/4 down-regulation in rats.","volume":"1717","author":"Yu","year":"2019","journal-title":"Brain Res."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1080\/10286020.2020.1846530","article-title":"Two new quinochalcone glycosides from the safflower yellow pigments.","volume":"22","author":"Zhang","year":"2020","journal-title":"J. Asian Nat. Prod. Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"L960","DOI":"10.1152\/ajplung.00388.2006","article-title":"Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-kappaB.","volume":"292","author":"Zhang","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.neulet.2014.01.005","article-title":"Hydroxy-safflor yellow A inhibits neuroinflammation mediated by A\u03b21\u201342 in BV-2 cells.","volume":"562","author":"Zhang","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/692302","article-title":"The effect of safflower yellow on spinal cord ischemia reperfusion injury in rabbits.","volume":"2013","author":"Zhou","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"B97","doi-asserted-by":"publisher","first-page":"520","DOI":"10.3892\/etm.2017.5414","article-title":"The effect of hydroxy safflower yellow A on coronary heart disease through Bcl-2\/Bax and PPAR-\u03b3.","volume":"15","author":"Zhou","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00127","article-title":"The mechanism by which safflower yellow decreases body fat mass and improves insulin sensitivity in HFD-induced obese mice.","volume":"7","author":"Zhu","year":"2016","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.803885\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T04:37:30Z","timestamp":1640320650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2021.803885\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":98,"alternative-id":["10.3389\/fnins.2021.803885"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2021.803885","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]},"article-number":"803885"}}