{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:02:12Z","timestamp":1793026932883,"version":"4.5.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1016\/j.phymed.2023.154712","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T02:29:27Z","timestamp":1675823367000},"page":"154712","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"special_numbering":"C","title":["Brain regional pharmacokinetics of hydroxytyrosol and its molecular mechanism against depression assessed by multi-omics approaches"],"prefix":"10.1016","volume":"112","author":[{"given":"Li","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7500-9275","authenticated-orcid":false,"given":"Xiaobo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2023.154712_bib0001","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12013-013-9750-1","article-title":"Citric acid cycle and role of its intermediates in metabolism","volume":"68","author":"Akram","year":"2014","journal-title":"Cell Biochem. Biophys."},{"key":"10.1016\/j.phymed.2023.154712_bib0002","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jbiotec.2019.12.016","article-title":"Hydroxytyrosol: a natural compound with promising pharmacological activities","volume":"309","author":"Bertelli","year":"2020","journal-title":"J. Biotechnology"},{"issue":"4","key":"10.1016\/j.phymed.2023.154712_bib0003","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s11745-014-3882-y","article-title":"Microglial cell activation increases saturated and decreases monounsaturated fatty acid content, but both lipid species are proinflammatory","volume":"49","author":"Button","year":"2014","journal-title":"Lipids"},{"issue":"1","key":"10.1016\/j.phymed.2023.154712_bib0004","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12974-017-0917-3","article-title":"Omega\u20133 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1\/TLR4\/NF\u2013\u03baB pathway following experimental traumatic brain injury","volume":"14","author":"Chen","year":"2017","journal-title":"J. Neuroinflammation"},{"issue":"1","key":"10.1016\/j.phymed.2023.154712_bib0005","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12974-020-01742-3","article-title":"Role of dietary fatty acids in microglial polarization in Alzheimer's disease","volume":"17","author":"Desale","year":"2020","journal-title":"J. Neuroinflammation"},{"issue":"16","key":"10.1016\/j.phymed.2023.154712_bib0006","doi-asserted-by":"crossref","first-page":"8542","DOI":"10.1039\/D2FO01357F","article-title":"Integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology to probe distinctions between the stems of Cistanche deserticola and C. tubulosa based on antidepressant activity","volume":"13","author":"Fan","year":"2022","journal-title":"Food Funct."},{"key":"10.1016\/j.phymed.2023.154712_bib0007","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2021.153471","article-title":"Total glycosides from stems of Cistanche tubulosa alleviate depression\u2013like behaviors: bidirectional interaction of the phytochemicals and gut microbiota","volume":"83","author":"Fan","year":"2021","journal-title":"Phytomedicine"},{"issue":"5","key":"10.1016\/j.phymed.2023.154712_bib0008","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1021\/acs.jproteome.0c00940","article-title":"Comprehensive analysis strategy of nervous\u2013endocrine\u2013immune\u2013related metabolites to evaluate arachidonic acid as a novel diagnostic biomarker in depression","volume":"20","author":"Gao","year":"2021","journal-title":"J. Proteome Res."},{"issue":"1","key":"10.1016\/j.phymed.2023.154712_bib0009","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1037\/0735-7044.122.1.16","article-title":"The interactions and dissociations of the dorsal hippocampus subregions: how the dentate gyrus, CA3, and CA1 process spatial information","volume":"122","author":"Goodrich\u2013Hunsaker","year":"2008","journal-title":"Behav. Neurosci."},{"issue":"7","key":"10.1016\/j.phymed.2023.154712_bib0010","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/mnfr.201500048","article-title":"Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats","volume":"59","author":"Hazas","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"issue":"2","key":"10.1016\/j.phymed.2023.154712_bib0011","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.tins.2020.10.003","article-title":"Neuroprotective versus neuroinflammatory roles of complement: from development to disease","volume":"44","author":"Kanmogne","year":"2021","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.phymed.2023.154712_bib0012","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2018.06.033","article-title":"Blood-brain barrier regulation in psychiatric disorders","volume":"726","author":"Kealy","year":"2020","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.phymed.2023.154712_bib0013","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1021\/acs.jafc.7b02829","article-title":"Human gastrointestinal metabolism of the Cistanches Herba water extract in vitro: elucidation of the metabolic profile based on comprehensive metabolite identification in gastric juice, intestinal juice, human intestinal bacteria, and intestinal microsomes","volume":"65","author":"Li","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.phymed.2023.154712_bib0014","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.brainresbull.2020.07.004","article-title":"hUC\u2013MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling\u2013mediated microglial polarization during astrocyte\u2013microglia crosstalk","volume":"163","author":"Li","year":"2020","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.phymed.2023.154712_bib0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2019.112243","article-title":"Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway","volume":"246","author":"Liang","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2023.154712_bib0016","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12868-021-00641-4","article-title":"Causal relationship of CA3 back\u2013projection to the dentate gyrus and its role in CA1 fast ripple generation","volume":"22","author":"N\u00fa\u00f1ez\u2013Ochoa","year":"2021","journal-title":"BMC Neurosci."},{"issue":"5","key":"10.1016\/j.phymed.2023.154712_bib0017","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.3390\/ijms21051769","article-title":"EPA is more effective than DHA to improve depression\u2013like behavior, glia cell dysfunction and hippcampal apoptosis signaling in a chronic stress induced rat model of depression","volume":"21","author":"Peng","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2023.154712_bib0018","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.neubiorev.2015.07.015","article-title":"Sickness: from the focus on cytokines, prostaglandins, and complement factors to the perspectives of neurons","volume":"57","author":"Poon","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.phymed.2023.154712_bib0019","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/bs.apha.2021.03.004","article-title":"Neuroimmunology of depression","volume":"91","author":"Sarno","year":"2021","journal-title":"Adv. Pharmacol."},{"issue":"6","key":"10.1016\/j.phymed.2023.154712_bib0020","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.biopsych.2009.11.005","article-title":"Phospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon\u2013alpha\u2013induced depression by regulating polyunsaturated fatty acids levels","volume":"67","author":"Su","year":"2010","journal-title":"Biol. Psychiatry"},{"issue":"1","key":"10.1016\/j.phymed.2023.154712_bib0021","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1073\/pnas.1808950116","article-title":"Spatially resolved metabolomics to discover tumor\u2013associated metabolic alterations","volume":"116","author":"Sun","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"9","key":"10.1016\/j.phymed.2023.154712_bib0022","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.3390\/nu14091882","article-title":"Short-chain fatty acids ameliorate depressive-like behaviors of high fructose-fed mice by rescuing hippocampal neurogenesis decline and blood-brain barrier damage","volume":"14","author":"Tang","year":"2022","journal-title":"Nutrients"},{"issue":"6","key":"10.1016\/j.phymed.2023.154712_bib0023","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.apsb.2019.12.004","article-title":"In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging","volume":"10","author":"Wang","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"issue":"11","key":"10.1016\/j.phymed.2023.154712_bib0024","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1016\/j.apsb.2021.05.013","article-title":"Spatial\u2013resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.phymed.2023.154712_bib0025","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbi.2021.09.005","article-title":"Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder","volume":"99","author":"Westacott","year":"2022","journal-title":"Brain Behav. Immun."},{"issue":"16","key":"10.1016\/j.phymed.2023.154712_bib0026","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1016\/j.chroma.2008.10.116","article-title":"Measurement of free hydroxytyrosol in microdialysates from blood and brain of anesthetized rats by liquid chromatography with fluorescence detection","volume":"1216","author":"Wu","year":"2009","journal-title":"J. Chromatogr. A."},{"key":"10.1016\/j.phymed.2023.154712_bib0027","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","article-title":"Microglia in physiology and disease","volume":"79","author":"Wolf","year":"2017","journal-title":"Annu. Rev. Physiol."},{"issue":"1","key":"10.1016\/j.phymed.2023.154712_bib0028","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12974-021-02309-6","article-title":"The semantics of microglia activation: neuroinflammation, homeostasis, and stress","volume":"18","author":"Woodburn","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.phymed.2023.154712_bib0029","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/8861903","article-title":"Changes in hippocampal plasticity in depression and therapeutic approaches influencing these changes","volume":"2020","author":"Xu","year":"2020","journal-title":"Neural Plast."},{"key":"10.1016\/j.phymed.2023.154712_bib0030","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3389\/fnins.2019.00247","article-title":"Integrated metabolomics and proteomics analysis revealed second messenger system disturbance in hippocampus of chronic social defeat stress rat","volume":"13","author":"Yang","year":"2019","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.phymed.2023.154712_bib0031","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.phymed.2017.12.002","article-title":"Plasma pharmacokinetics and cerebral nuclei distribution of major constituents of Psoraleae fructus in rats after oral administration","volume":"38","author":"Yang","year":"2018","journal-title":"Phytomedicine"},{"issue":"6","key":"10.1016\/j.phymed.2023.154712_bib0032","doi-asserted-by":"crossref","first-page":"G1081","DOI":"10.1152\/ajpgi.00123.2021","article-title":"Amygdala microglia modify neuronal plasticity via complement C1q\/C3\u2013CR3 signaling and contribute to visceral pain in a rat model","volume":"320","author":"Yuan","year":"2021","journal-title":"Am. J. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.phymed.2023.154712_bib0033","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1002\/jssc.202000625","article-title":"Pharmacokinetic comparison of nine bioactive components in rat plasma following oral administration of raw and wine-processed Ligustri Lucidi Fructus by ultra\u2013high\u2013performance liquid chromatography coupled with triple quadrupole mass spectrometry","volume":"43","author":"Zhang","year":"2020","journal-title":"J. Sep. Sci."},{"key":"10.1016\/j.phymed.2023.154712_bib0034","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroscience.2017.12.001","article-title":"Integrated metabolomics and proteomics analysis of hippocampus in a rat model of depression","volume":"371","author":"Zhang","year":"2018","journal-title":"Neuroscience"},{"key":"10.1016\/j.phymed.2023.154712_bib0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.154453","article-title":"An anticomplement homogeneous polysaccharide from Hedyotis diffusa attenuates lipopolysaccharide-induced acute lung injury and inhibits neutrophil extracellular trap formation","volume":"107","author":"Zhang","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2023.154712_bib0036","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13578-022-00832-4","article-title":"IL-1R\/C3aR signaling regulates synaptic pruning in the prefrontal cortex of depression","volume":"12","author":"Zhang","year":"2022","journal-title":"Cell Biosci."},{"issue":"12","key":"10.1016\/j.phymed.2023.154712_bib0037","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1039\/D1FO00210D","article-title":"Hydroxytyrosol alleviates oxidative stress and neuroinflammation and enhances hippocampal neurotrophic signaling to improve stress\u2013induced depressive behaviors in mice","volume":"12","author":"Zhao","year":"2021","journal-title":"Food Funct."},{"key":"10.1016\/j.phymed.2023.154712_bib0038","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.bbr.2018.07.001","article-title":"Minocycline ameliorates depressive behaviors and neuro\u2013immune dysfunction induced by chronic unpredictable mild stress in the rat","volume":"356","author":"Zhang","year":"2019","journal-title":"Behav. Brain Res."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323000703?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711323000703?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:43:35Z","timestamp":1760553815000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711323000703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":38,"alternative-id":["S0944711323000703"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2023.154712","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Brain regional pharmacokinetics of hydroxytyrosol and its molecular mechanism against depression assessed by multi-omics approaches","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2023.154712","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"154712"}}