{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:17:01Z","timestamp":1788257821106,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Space Medical Experiment Project of China Manned Space Program","award":["HYZHXM02003"],"award-info":[{"award-number":["HYZHXM02003"]}]},{"DOI":"10.13039\/501100003472","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["HIT-XTCX-5"],"award-info":[{"award-number":["HIT-XTCX-5"]}],"id":[{"id":"10.13039\/501100003472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Fractional ionizing radiation (FIR) is a standard cancer therapy but often induces severe central nervous system complications, including cognitive decline and physiological dysfunction. While natural flavonoids hold therapeutic promise for radiation-induced brain injury (RIBI), optimizing their combinations and elucidating the underlying molecular pathways remain challenging. Methods: To develop a precise therapeutic strategy, we first integrated network pharmacology and UHPLC-Q-Orbitrap MS\/MS analysis to identify three highly effective flavonoid monomers from a radioprotective botanical extract. Subsequently, an in vivo anti-inflammatory screening was conducted to determine the optimal combinatorial ratio, designated as the ternary formulation QLI. The neuroprotective efficacy of QLI was then systematically evaluated in a mouse model of fractional RIBI (cumulative dose of 12 Gy) through behavioral assessments, hematopoietic profiling, and neurotransmitter analyses. Transcriptomic alterations were explored via RNA-sequencing (RNA-seq) and validated by molecular docking, RT-qPCR, and Western blotting. Results: Pharmacological and mass spectrometry analyses identified Quercetin, Luteolin, and Isorhamnetin-3-O-glucoside as the core bioactive monomers. Quantitative synergistic screening established the optimal QLI formulation at a mass ratio of 2:1:1. In vivo, FIR exposure induced severe spatial memory deficits, disrupted neurotransmitter homeostasis, and caused hematopoietic decline. Administration of QLI successfully reversed these physiological and cognitive impairments. Transcriptomic profiling revealed that QLI globally reprogrammed aberrant gene expression, specifically normalizing signaling networks related to the PI3K\u2013Akt pathway, apoptosis, and neuroactive ligand\u2013receptor interactions. Multidimensional validation confirmed that QLI mitigated neuroinflammation, suppressed astrocyte hyperactivation (GFAP), and preserved synaptic plasticity by preventing the pathological accumulation of SynGAP and autophagic stress (Beclin-1). Conclusions: The rationally designed ternary flavonoid formulation (QLI) provides potent neuroprotection against fractional RIBI. By resolving neuroinflammation, alleviating synaptic plasticity suppression, and normalizing stress-induced transcriptomic disruptions, QLI represents a promising multi-target experimental formulation with the potential to mitigate radiotherapy-associated neurological side effects.<\/jats:p>","DOI":"10.3390\/ijms27177721","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Ternary Flavonoid Formulation Mitigates Fractional Radiation-Induced Brain Injury via Transcriptomic Reprogramming and Synaptic Protection"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuanbing","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"},{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishu","family":"Yin","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"},{"name":"Zhengzhou Advanced Research Institute, Harbin Institute of Technology, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ju","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"},{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heqi","family":"Gao","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China"},{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangjing","family":"Miao","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"},{"name":"Zhengzhou Advanced Research Institute, Harbin Institute of Technology, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Lu","sequence":"additional","affiliation":[{"name":"National and Local Joint Engineering Laboratory for Synthesis, Harbin Institute of Technology, Harbin 150001, China"},{"name":"Zhengzhou Advanced Research Institute, Harbin Institute of Technology, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","first-page":"421","article-title":"Fractionation of radiation treatment in acoustics. Rationale and evidence in comparison to radiosurgery","volume":"50","author":"Flickinger","year":"2004","journal-title":"Neuro-Chirurgie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.jmir.2016.06.006","article-title":"An Overview of Radiation-Induced Nausea and Vomiting","volume":"47","author":"Rowbottom","year":"2016","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105875","DOI":"10.1016\/j.tifs.2026.105875","article-title":"Engineering food systems for microbiome stability and metabolic health in deep-space missions","volume":"175","author":"Gao","year":"2026","journal-title":"Trends Food Sci. Technol."},{"key":"ref_4","first-page":"10","article-title":"Radiation-induced brain injury: Current concepts and therapeutic strategies targeting neuroinflammation","volume":"2","author":"Turnquist","year":"2020","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/09553002.2022.2074167","article-title":"Neurocognitive and radiological changes after cranial radiation therapy in humans and rodents: A systematic review","volume":"99","author":"Perez","year":"2023","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13045-020-00881-7","article-title":"Emerging therapeutic agents for advanced non-small cell lung cancer","volume":"13","author":"Chen","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, X., Wang, L., He, C., Shi, Z., Fu, Q., Xu, W., Zhang, S., and Hu, S. (2021). Review of the Efficacy and Mechanisms of Traditional Chinese Medicines as a Therapeutic Option for Ionizing Radiation Induced Damage. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.617559"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jns.2007.01.014","article-title":"Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: A potential rat model of vascular dementia","volume":"257","author":"Brown","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/pcmedi\/pbz022","article-title":"Translating current biomedical therapies for long duration, deep space missions","volume":"2","author":"Iosim","year":"2019","journal-title":"Precis. Clin. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.4172\/2167-7964.1000283","article-title":"Effect of Gamma Ray on Reactive Oxygen Species at Experimental Animals","volume":"6","author":"Km","year":"2017","journal-title":"OMICS J. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7150\/ijms.3635","article-title":"Cancer and Radiation Therapy: Current Advances and Future Directions","volume":"9","author":"Baskar","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16196","DOI":"10.1039\/D0RA01017K","article-title":"Simulated spatial radiation impacts learning and memory ability with alterations of neuromorphology and gut microbiota in mice","volume":"10","author":"Song","year":"2020","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1007\/s00210-024-03622-6","article-title":"Natural products as drug leads: Exploring their potential in drug discovery and development","volume":"398","author":"Singh","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"138453","DOI":"10.1016\/j.foodchem.2024.138453","article-title":"Comparison of binding sites and affinity of flavonol\u2013Cu(II) complexes with the same parent nucleus: Synthesis, DFT prediction, and coordination pattern","volume":"442","author":"Guan","year":"2024","journal-title":"Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105213","DOI":"10.1016\/j.fbio.2024.105213","article-title":"Mechanism of flavonols for binding protein and inhibiting cell activity: Regulation by B-ring hydroxyl groups and Cu(II) coordination","volume":"62","author":"Guan","year":"2024","journal-title":"Food Biosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/jrr\/rrs080","article-title":"Radio-protective effect of catalpol in cultured cells and mice","volume":"54","author":"Chen","year":"2013","journal-title":"J. Radiat. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, J.R., Zhong, K.X., Qin, S.Q., Jing, Y.Q., Liu, S.M., Li, D., and Peng, C. (2023). Astragalin: A food-origin flavonoid with therapeutic effect for multiple diseases. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1265960"},{"key":"ref_18","first-page":"e380723","article-title":"Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2\/HO-1 signaling pathway","volume":"38","author":"Zhang","year":"2023","journal-title":"Acta Cir. Bras."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1667\/RADE-22-00090.1","article-title":"Quercetin Mitigates Radiation-Induced Intestinal Injury and Promotes Intestinal Regeneration via Nrf2-Mediated Antioxidant Pathway","volume":"199","author":"Zhu","year":"2023","journal-title":"Radiat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wen, L., Zhang, W., Hu, J., Chen, T., Wang, Y., Lv, C., Li, M., Wang, L., and Xiao, F. (2024). Luteolin target HSPB1 regulates endothelial cell ferroptosis to protect against radiation vascular injury. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0311922"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nishiyama, Y., Morita, A., Tatsuta, S., Kanamaru, M., Sakaue, M., Ueda, K., Shono, M., Fujita, R., Wang, B., and Hosoi, Y. (2021). Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome. Genes, 12.","DOI":"10.3390\/genes12101514"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116306","DOI":"10.1016\/j.jep.2023.116306","article-title":"Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula","volume":"309","author":"Zhao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116941","DOI":"10.1016\/j.jep.2023.116941","article-title":"The neuroprotective mechanisms of naringenin: Inhibition of apoptosis through the PI3K\/AKT pathway after hypoxic-ischemic brain damage","volume":"318","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"He","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cui, Y.-F., Zhang, W.-W., Li, Y.-N., Xu, J., Lan, X.-M., Song, S.-Y., Lin, Y.-Q., Dai, L., and Zhang, J.-Y. (2022). The Analytical Strategy of \u201cIon Induction and Deduction Based on Net-Hubs\u201d for the Comprehensive Characterization of Naringenin Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Orbitrap Mass Spectrometer. Molecules, 27.","DOI":"10.3390\/molecules27217282"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/jat.904","article-title":"Genistein treatment protects mice from ionizing radiation injury","volume":"23","author":"Landauer","year":"2003","journal-title":"J. Appl. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s00018-018-2987-5","article-title":"Adaptive responses to low doses of radiation or chemicals: Their cellular and molecular mechanisms","volume":"76","author":"Bontemps","year":"2019","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.freeradbiomed.2003.11.023","article-title":"Flavonoid permeability across an in situ model of the blood\u2013brain barrier","volume":"36","author":"Youdim","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.freeradbiomed.2011.06.017","article-title":"Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats","volume":"51","author":"Ishisaka","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11456","DOI":"10.1038\/s41598-017-11512-6","article-title":"Polyphenols journey through blood-brain barrier towards neuronal protection","volume":"7","author":"Figueira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","first-page":"201","article-title":"Effect of Loranthus longiflorus ethanolic Extract on Neuronal Damage Induced by Electromagnetic Radiation in Wistar Rats","volume":"56","author":"Gouthaman","year":"2022","journal-title":"Indian J. Anim. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1093\/jrr\/rrab026","article-title":"Neurobehavioral effects of acute low-dose whole-body irradiation","volume":"62","author":"Bekal","year":"2021","journal-title":"J. Radiat. Res."},{"key":"ref_33","first-page":"57","article-title":"Neuroprotective effects of umbilical cord-derived mesenchymal stem cells on radiation-induced brain injury in mice","volume":"50","author":"Wang","year":"2020","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1667\/RR3206","article-title":"Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis","volume":"162","author":"Raber","year":"2004","journal-title":"Radiat. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/nm749","article-title":"Irradiation induces neural precursor-cell dysfunction","volume":"8","author":"Monje","year":"2002","journal-title":"Nat. Med."},{"key":"ref_36","first-page":"80","article-title":"Does occupational ionizing radiation exposure in healthcare workers affect their hematological parameters?","volume":"78","author":"Kurtul","year":"2022","journal-title":"Arch. Environ. Occup. Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100264","DOI":"10.1016\/j.bbih.2021.100264","article-title":"Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice","volume":"15","author":"Wolff","year":"2021","journal-title":"Brain Behav. Immun.-Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0094-5765(85)90072-4","article-title":"Serotonin in individual hypothalamic nuclei of rats after space flight on biosatellite cosmos 1129","volume":"12","author":"Serova","year":"1985","journal-title":"Acta Astronaut."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1055\/a-1686-9620","article-title":"Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer\u2019s Disease Prevention","volume":"55","author":"Nykamp","year":"2022","journal-title":"Pharmacopsychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"374","DOI":"10.15171\/apb.2019.044","article-title":"5-HIAA as a Potential Biological Marker for Neurological and Psychiatric Disorders","volume":"9","author":"Jayamohananan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/(SICI)1097-4547(19990315)55:6<770::AID-JNR11>3.0.CO;2-A","article-title":"Effect of neutron-gamma radiation on dopamine and serotonin metabolism in the rat brain: A regional analysis","volume":"55","author":"Foulon","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0094-5765(83)90080-2","article-title":"Catecholamines and their enzymes in discrete brain areas of rats after space flight on biosatellites Cosmos","volume":"10","author":"Serova","year":"1983","journal-title":"Acta Astronaut."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.cell.2020.10.050","article-title":"Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration","volume":"183","author":"Afshinnekoo","year":"2020","journal-title":"Cell"},{"key":"ref_44","first-page":"115","article-title":"Simulated space environmental factors of weightlessness, noise and low atmospheric pressure differentially affect the diurnal rhythm and the gut microbiome","volume":"40","author":"Gan","year":"2024","journal-title":"Life Sci. Space Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wu, X., Li, D., Liu, J., Diao, L., Ling, S., Li, Y., Gao, J., Fan, Q., Sun, W., and Li, Q. (2017). Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00315"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan metabolism in health and disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab."},{"key":"ref_47","first-page":"54","article-title":"Space radiation risks to the central nervous system","volume":"2","author":"Cucinotta","year":"2014","journal-title":"Life Sci. Space Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Raber, J., Torres, E.R.S., Akinyeke, T., Lee, J., Weber Boutros, S.J., Turker, M.S., and Kronenberg, A. (2018). Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041247"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/jrr\/rrab112","article-title":"Nicaraven mitigates radiation-induced lung injury by downregulating the NF-\u03baB and TGF-\u03b2\/Smad pathways to suppress the inflammatory response","volume":"2","author":"Xu","year":"2022","journal-title":"J. Radiat. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.15586\/qas.v17i3.1561","article-title":"Structural and Immunomodulatory Properties of Bioactive Polysaccharide from Solid-State Fermented Brown Rice with Antrodia Cinnamomea Mycelia","volume":"17","author":"Kaewkumsan","year":"2025","journal-title":"Qual. Assur. Saf. Crops Foods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1134\/S106235902312018X","article-title":"Ionizing Radiation and Inflammatory Reactions: Formation Mechanisms and Implications","volume":"50","author":"Ponomarev","year":"2023","journal-title":"Biol. Bull."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113270","DOI":"10.1016\/j.isci.2025.113270","article-title":"The elucidation of the dual role of Beclin-1 in ischemic stroke through systems biology modeling","volume":"28","author":"Cha","year":"2025","journal-title":"iScience"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10002","DOI":"10.70322\/iMed.2026.10002","article-title":"Roles of Astrocytes in Radiation-Induced Brain Injury: Pathophysiological Mechanisms and Therapeutic Strategies","volume":"1","author":"Liao","year":"2026","journal-title":"iMed"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eadk1291","DOI":"10.1126\/science.adk1291","article-title":"SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity","volume":"383","author":"Araki","year":"2024","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1523\/JNEUROSCI.0420-19.2020","article-title":"Twenty Years of SynGAP Research: From Synapses to Cognition","volume":"40","author":"Gamache","year":"2020","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.1021\/jf803579e","article-title":"Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic","volume":"57","author":"Ruiz","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cunningham, P., Patton, E., VanderVeen, B., Unger, C., Aladhami, A., Enos, R., Madero, S., Chatzistamou, I., Fan, D., and Murphy, E. (2022). Sub-chronic oral toxicity screening of quercetin in mice. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03758-z"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"bbaf354","DOI":"10.1093\/bib\/bbaf354","article-title":"Applications and techniques of single-cell RNA sequencing across diverse species","volume":"26","author":"Woo","year":"2025","journal-title":"Brief. Bioinform."},{"key":"ref_59","first-page":"486","article-title":"Mechanism of Yiqi Jiedu Formula in alleviating radiation-induced energy supply impairment in Sertoli cells via PI3K\/Akt-mediated glycolysis","volume":"49","author":"Zhang","year":"2026","journal-title":"J. Beijing Univ. Tradit. Chin. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, Q., Hu, J., Wang, C., Wan, D., Li, Q., Jiang, Q., Du, L., and Jin, Y. (2022). Nasal Delivery of Cinnarizine Thermo- and Ion-Sensitive In Situ Hydrogels for Treatment of Microwave-Induced Brain Injury. Gels, 8.","DOI":"10.3390\/gels8020108"},{"key":"ref_61","first-page":"408","article-title":"Quantitative study of the rapeutic effects of a Chinese medicine, Anduolin capsule, on the long-term injury in rats induced by micowave exposure","volume":"20","author":"Zhang","year":"2015","journal-title":"Chin. J. Stereol."},{"key":"ref_62","first-page":"205","article-title":"Effects of anduolin on some immune and reproductive functions in electromagnetic irradiated mice","volume":"34","author":"Lv","year":"2007","journal-title":"China Occup. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10211","DOI":"10.1523\/JNEUROSCI.4868-11.2012","article-title":"Directional responding of C57BL\/6J mice in the Morris water maze is influenced by visual and vestibular cues and is dependent on the anterior thalamic nuclei","volume":"32","author":"Stackman","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.neubiorev.2004.06.006","article-title":"The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory","volume":"28","author":"Hughes","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jchromb.2019.02.021","article-title":"LC-MS\/MS-based quantification of tryptophan metabolites and neurotransmitters in the serum and brain of mice","volume":"1112","author":"Wang","year":"2019","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:50:59Z","timestamp":1788256259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":67,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177721"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177721","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}