{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:47:03Z","timestamp":1792784823466,"version":"4.5.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370926"],"award-info":[{"award-number":["82370926"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["24JRRA188"],"award-info":[{"award-number":["24JRRA188"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["24JRRA943"],"award-info":[{"award-number":["24JRRA943"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stomatological Hospital, Lanzhou University","award":["Lzukqky-9-y13"],"award-info":[{"award-number":["Lzukqky-9-y13"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Gansu Provincial Joint Scientific Research Fund","award":["24JRRA941"],"award-info":[{"award-number":["24JRRA941"]}]},{"name":"Gansu Health Industry Research Project","award":["GSWSKY2025-34"],"award-info":[{"award-number":["GSWSKY2025-34"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Radiation-induced brain injury (RIBI) is a common side effect of cranial radiotherapy that severely impairs patients\u2019 neurological function and quality of life. Currently, effective and safe remedies for RIBI remain limited. Paeoniflorin (PF), a key component of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora, is a traditional Chinese herbal compound with well-documented anti-inflammatory, antioxidant, and neuroprotective benefits. Our prior research demonstrated that TGP alleviates RIBI; however, its deeper protective mechanisms are still unknown. Purpose: The purpose of this study was to investigate the protective mechanisms of TGP against RIBI, focusing on the effects of PF on microglial polarization. Methods: In vivo, we assessed the effects of TGP on microglial polarization using immunofluorescence colocalization analysis. In vitro, we evaluated the effects of PF on microglial polarization through CCK-8, qRT-PCR, flow cytometry, Western blot, and ELISA. Additionally, we utilized network pharmacology, molecular docking, and molecular dynamics simulations, together with qRT-PCR and Western blotting, to investigate the key pathway molecules involved in PF\u2019s modulation of microglial polarization. Results: In vivo, TGP attenuated radiation-induced alterations in microglial polarization by decreasing the expression of M1-associated markers and increasing the expression of M2-associated markers. Consistently, PF modulated radiation-induced BV2 cell polarization by decreasing the level of M1-associated marker expression and increasing the level of M2-associated marker expression. Mechanistic analyses suggest that ERK signaling may be involved in the regulation of microglial polarization induced by the PF. Conclusion: TGP and its major bioactive component, PF, may attenuate RIBI by modulating microglial polarization, with the ERK signaling pathway potentially involved in this process, supporting the potential of PF as a candidate strategy for RIBI.<\/jats:p>","DOI":"10.1021\/acsomega.6c03490","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:02:04Z","timestamp":1790042524000},"page":"58820-58835","source":"Crossref","is-referenced-by-count":0,"title":["Paeoniflorin Attenuates\nRadiation-Induced Brain Injury\nAssociated with Modulation of Microglial Polarization and ERK\/MAPK\nSignaling"],"prefix":"10.1021","volume":"11","author":[{"given":"Zhongfang","family":"Zhao","sequence":"first","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoju","family":"Chen","sequence":"additional","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"He","sequence":"additional","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Institute of Modern Physics, Chinese Academy of Sciences , ,","place":["Lanzhou, China, 730000"]},{"name":"Advanced Energy Science and Technology Guangdong Laboratory , ,","place":["Huizhou, China, 516000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1186-1725","authenticated-orcid":true,"given":"Taofeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology , , ,","place":["Lanzhou, China, 730050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhencun","family":"Cui","sequence":"additional","affiliation":[{"name":"Lanzhou University , , ,","place":["Lanzhou, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics, Chinese Academy of Sciences , ,","place":["Lanzhou, China, 730000"]},{"name":"Advanced Energy Science and Technology Guangdong Laboratory , ,","place":["Huizhou, China, 516000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5684-9594","authenticated-orcid":true,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]},{"name":"Lanzhou University , , , ,","place":["Lanzhou, Gansu, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"21","key":"2026100610503962300_cit1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.179530","article-title":"All-trans retinoic acid inhibits glioblastoma progression and attenuates\nradiation-induced brain injury","volume":"9","author":"Fu","year":"2024","journal-title":"JCI Insight"},{"issue":"12","key":"2026100610503962300_cit2","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1016\/j.ymthe.2021.06.019","article-title":"Prior nasal delivery of antagomiR-122 prevents radiation-induced\nbrain injury","volume":"29","author":"Zhou","year":"2021","journal-title":"Mol. Ther."},{"issue":"1","key":"2026100610503962300_cit3","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02596-7","article-title":"Pregabalin mitigates\nmicroglial activation and neuronal injury by inhibiting HMGB1 signaling\npathway in radiation-induced brain injury","volume":"19","author":"Zhang","year":"2022","journal-title":"J.\nNeuroinflammation"},{"issue":"15","key":"2026100610503962300_cit4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158286","article-title":"Microglia\nas Therapeutic Target for Radiation-Induced Brain Injury","volume":"23","author":"Liu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"2026100610503962300_cit5","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.ijrobp.2021.07.007","article-title":"Fractionated\nLow-Dose Radiation Induces Long-Lasting Inflammatory Responses in\nthe Hippocampal Stem Cell Niche","volume":"111","author":"Schmal","year":"2021","journal-title":"Int. J. Radiat.\nOncol., Biol., Phys."},{"issue":"2","key":"2026100610503962300_cit6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.immuni.2026.01.007","article-title":"Microglia\nmakeover: On-demand control panel revamp","volume":"59","author":"Masuda","year":"2026","journal-title":"Immunity"},{"issue":"1","key":"2026100610503962300_cit7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02596-7","article-title":"Pregabalin mitigates\nmicroglial activation and neuronal injury by inhibiting HMGB1 signaling\npathway in radiation-induced brain injury","volume":"19","author":"Zhang","year":"2022","journal-title":"J.\nNeuroinflammation"},{"issue":"7","key":"2026100610503962300_cit8","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1038\/s41593-025-01931-4","article-title":"Microglia heterogeneity, modeling and cell-state annotation\nin development and neurodegeneration","volume":"28","author":"Fumagalli","year":"2025","journal-title":"Nat. Neurosci."},{"issue":"20","key":"2026100610503962300_cit9","doi-asserted-by":"publisher","first-page":"4761","DOI":"10.1111\/bph.16404","article-title":"Recent\nadvances in neuroinflammation prevention and therapy: the role of\nnatural products and underlying mechanisms based on molecular targets","volume":"182","author":"Zhao","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"2026100610503962300_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102160","article-title":"Modulating\nthe polarization phenotype of microglia - A valuable strategy\nfor central nervous system diseases","volume":"93","author":"Long","year":"2024","journal-title":"Ageing\nRes. 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Ther."},{"key":"2026100610503962300_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153835","article-title":"Paeoniflorin\nameliorates airway inflammation and immune response in ovalbumin induced\nasthmatic mice: From oxidative stress to autophagy","volume":"96","author":"Han","year":"2022","journal-title":"Phytomedicine"},{"key":"2026100610503962300_cit15","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154901","article-title":"Paeoniflorin suppresses\nkidney inflammation by regulating macrophage polarization via KLF4-mediated\nmitophagy","volume":"116","author":"Cao","year":"2023","journal-title":"Phytomedicine"},{"key":"2026100610503962300_cit16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116772","article-title":"Antioxidant effects\nof Paeoniflorin and relevant molecular mechanisms as related to a\nvariety of diseases: A review","volume":"176","author":"Lu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"2026100610503962300_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107965","article-title":"Paeoniflorin as\na potential therapeutic\nagent for cerebrovascular diseases: A comprehensive review","volume":"221","author":"Wang","year":"2025","journal-title":"Pharmacol. Res."},{"issue":"4","key":"2026100610503962300_cit18","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2024-101979","article-title":"Paeoniflorin ameliorates\ndepressive behaviours by modulating microbiota-gut-brain\naxis functions","volume":"38","author":"Zhang","year":"2025","journal-title":"Gen. Psychiatry"},{"key":"2026100610503962300_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153669","article-title":"Paeoniflorin: A neuroprotective\nmonoterpenoid glycoside with promising\nanti-depressive properties","volume":"90","author":"Wang","year":"2021","journal-title":"Phytomedicine"},{"issue":"6","key":"2026100610503962300_cit20","doi-asserted-by":"publisher","first-page":"593","DOI":"10.4162\/nrp.2020.14.6.593","article-title":"Paeoniflorin\nameliorates A\u03b2-stimulated\nneuroinflammation via regulation of NF-\u03baB signaling pathway\nand A\u03b2 degradation in C6 glial cells","volume":"14","author":"Cho","year":"2020","journal-title":"Nutr. Res. Pract."},{"key":"2026100610503962300_cit21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578180","article-title":"Microglia\nmediated neuroinflammation in neurodegenerative diseases: A review\non the cell signaling pathways involved in microglial activation","volume":"383","author":"Biswas","year":"2023","journal-title":"J. Neuroimmunol."},{"issue":"1","key":"2026100610503962300_cit22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-38137-y","article-title":"Esketamine attenuates bone cancer pain by suppressing\nMAPK signaling and glial activation in the spinal dorsal horn of rats","volume":"16","author":"Cheng","year":"2026","journal-title":"Sci. Rep."},{"key":"2026100610503962300_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114178","article-title":"Investigation of the effects and\nmechanism of Total Glycosides of paeony against Radiation-Induced\nbrain injury through network Pharmacology, molecular docking and experimental\nVerification","volume":"148","author":"Zhao","year":"2025","journal-title":"Int. Immunopharmacol."},{"issue":"1","key":"2026100610503962300_cit24","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-024-03024-9","article-title":"Blocking the\nMIF-CD74 axis augments radiotherapy efficacy for brain metastasis\nin NSCLC via synergistically promoting microglia M1 polarization","volume":"43","author":"Liu","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"10","key":"2026100610503962300_cit25","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305989","article-title":"Boosting Microglial Lipid Metabolism via TREM2 Signaling\nby Biomimetic Nanoparticles to Attenuate the Sevoflurane-Induced Developmental\nNeurotoxicity","volume":"11","author":"Li","year":"2024","journal-title":"Adv. Sci."},{"issue":"5","key":"2026100610503962300_cit26","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.neuron.2023.02.005","article-title":"Microglia as drivers of neurodegeneration:\nThe role\nof innate-adaptive immune signaling","volume":"111","author":"Kumari","year":"2023","journal-title":"Neuron"},{"issue":"5","key":"2026100610503962300_cit27","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1007\/s10753-024-01997-5","article-title":"Quercetin Regulates\nMicroglia M1\/M2 Polarization and Alleviates Retinal\nInflammation via ERK\/STAT3 Pathway","volume":"47","author":"Zou","year":"2024","journal-title":"Inflammation"},{"issue":"4","key":"2026100610503962300_cit28","doi-asserted-by":"publisher","DOI":"10.1177\/15593258251382964","article-title":"Lycium\nbarbarum Polysaccharides Suppress Radiation-Induced Microglial Inflammation\nby Inhibiting the IKK\u03b2\/I\u03baB\u03b1\/NF-\u03baB Pathway","volume":"23","author":"Zhang","year":"2025","journal-title":"Dose-Response"},{"issue":"3","key":"2026100610503962300_cit29","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1007\/s12035-020-02138-3","article-title":"Neuroprotective Effect\nof Fractalkine\non Radiation-induced Brain Injury Through Promoting the M2 Polarization\nof Microglia","volume":"58","author":"Wang","year":"2021","journal-title":"Mol. Neurobiol."},{"issue":"7","key":"2026100610503962300_cit30","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1111\/cns.13839","article-title":"Atractylenolide\nIII ameliorates spinal cord injury in rats by modulating\nmicroglial\/macrophage polarization","volume":"28","author":"Xue","year":"2022","journal-title":"CNS Neurosci.\nTher."},{"issue":"4","key":"2026100610503962300_cit31","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1002\/ptr.70217","article-title":"Cycloastragenol Alleviates Bone Cancer\nPain by Targeting Sirt1 to Inhibit Neuronal Ferroptosis and Promote\nM2Microglial Polarization in the Spinal Dorsal Horn of Rats","volume":"40","author":"Xu","year":"2026","journal-title":"Phytother. Res."},{"key":"2026100610503962300_cit32","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5801453","article-title":"An In Vitro\nVerification of the Effects of Paeoniflorin on Lipopolysaccharide-Exposed\nMicroglia","volume":"2020","author":"Chen","year":"2020","journal-title":"Evid. Based Complement. Alternat.\nMed."},{"key":"2026100610503962300_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115351","article-title":"Paeoniflorin attenuates\nneuropathic Pain-associated depression by modulating microglial M1\npolarization and correcting kynurenine pathway dysregulation","volume":"164","author":"Cheng","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"2026100610503962300_cit34","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-024-01056-z","article-title":"Network pharmacology:\na crucial approach\nin traditional Chinese medicine research","volume":"20","author":"Zhai","year":"2025","journal-title":"Chin.\nMed."},{"issue":"1","key":"2026100610503962300_cit35","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01306-x","article-title":"Carbon dioxide\nand MAPK signalling: towards therapy for inflammation","volume":"21","author":"Ga\u0142gan\u0301ska","year":"2023","journal-title":"Cell Commun. Signaling"},{"issue":"6","key":"2026100610503962300_cit36","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14794","article-title":"Microglia in radiation-induced brain injury: Cellular\nand molecular\nmechanisms and therapeutic potential","volume":"30","author":"Wang","year":"2024","journal-title":"CNS Neurosci.\nTher."},{"issue":"5","key":"2026100610503962300_cit37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036739","article-title":"Radiation-induced c-Jun activation\ndepends on MEK1-ERK1\/2 signaling pathway in microglial cells","volume":"7","author":"Deng","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"2026100610503962300_cit38","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1002\/jnr.24829","article-title":"Extracellular\nsignal-regulated kinase regulates microglial immune responses in Alzheimer\u2019s\ndisease","volume":"99","author":"Chen","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"2026100610503962300_cit39","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.115135","article-title":"Astragaloside\nIV confers neuroprotection against radiation-induced neuronal senescence\nvia the ERK pathway","volume":"386","author":"Ding","year":"2025","journal-title":"Exp. Neurol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c03490","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/39\/58820\/68588752\/acsomega.6c03490.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/39\/58820\/68588752\/acsomega.6c03490.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:11:29Z","timestamp":1791299489000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/39\/58820\/5434783\/Paeoniflorin-Attenuates-Radiation-Induced-Brain"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":39,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,10,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c03490","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}