{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:05:23Z","timestamp":1785434723906,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Burapha University (BUU), Thailand Science Research and Innovation (TSRI), and National Science Research and Innovation Fund","award":["2.78\/2569"],"award-info":[{"award-number":["2.78\/2569"]}]},{"name":"Full-time Researcher Fellowship Award from Burapha University","award":["PostGrad2568\/01"],"award-info":[{"award-number":["PostGrad2568\/01"]}]},{"award":["PostGrad2568\/01"],"award-info":[{"award-number":["PostGrad2568\/01"]}],"id":[{"id":"https:\/\/ror.org\/01ff74m36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation mediated by astrocyte\u2013microglia interactions plays a critical role in the progression of neurodegenerative disorders. Celastrus paniculatus (CP) seeds have long been associated with cognitive benefits; however, the chemical composition and anti-inflammatory potential of their high-polarity fractions remain poorly characterized. In this study, thin-layer chromatography (TLC)-derived high-polarity fractions (F6 and F7) from CP seeds were analyzed using untargeted LC\u2013MS\/MS metabolite profiling. After quality filtering, 99 metabolites were retained for classification, with enrichment of alkaloids and terpenoid-related compounds, including 41 structurally complex metabolites. To evaluate biological relevance, BV2 microglia were exposed to astrocyte-conditioned medium derived from H2O2-treated astrocytes (ACM-H), modeling sterile inflammatory signaling. ACM-H stimulation induced microglial activation characterized by morphological transformation, increased CD40 and inducible nitric oxide synthase (iNOS) expression, and elevated production of pro-inflammatory cytokines TNF-\u03b1 and IL-6. Co-treatment with CP fractions attenuated ACM-H-induced inflammatory responses, with fraction F7 showing stronger effects than F6. Fraction F7 showed stronger inhibitory effects on CD40 and iNOS expression, suppressed TNF-\u03b1 and IL-6 production, and partially restored ramified microglial morphology, whereas F6 exhibited comparable anti-inflammatory activity and showed a stronger effect on microglial phagocytic responses. Metabolomic analysis further indicated a higher relative abundance of terpenoid-related metabolites in F7. Collectively, these findings indicate that CP seed fractions, particularly F7, attenuate astrocyte-driven microglial activation in an in vitro sterile neuroinflammatory model.<\/jats:p>","DOI":"10.3390\/ijms27083551","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:14:46Z","timestamp":1776334486000},"page":"3551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TLC-Derived High-Polar Fractions of Celastrus paniculatus Seeds Attenuate Astrocyte-Driven Microglial Activation Through Suppression of CD40\/iNOS Signaling and Pro-Inflammatory Cytokines"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3659-976X","authenticated-orcid":false,"given":"Tanida","family":"Treerattanakulporn","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-9161","authenticated-orcid":false,"given":"Narongrit","family":"Thongon","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-6373","authenticated-orcid":false,"given":"Siriporn","family":"Chamniansawat","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adamu, A., Li, S., Gao, F., and Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: Current understanding and future therapeutic targets. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1347987"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s00401-021-02370-8","article-title":"Analyzing microglial phenotypes across neuropathologies: A practical guide","volume":"142","author":"Schwabenland","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Skrzypczak-Wiercioch, A., and Sa\u0142at, K. (2022). Lipopolysaccharide-induced model of neuroinflammation: Mechanisms of action, research application and future directions for its use. Molecules, 27.","DOI":"10.3390\/molecules27175481"},{"key":"ref_5","first-page":"8385961","article-title":"Sterile neuroinflammation and strategies for therapeutic intervention","volume":"2017","author":"Banjara","year":"2017","journal-title":"Int. J. Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/tox.23449","article-title":"Calycosin alleviates H2O2-induced astrocyte injury by restricting oxidative stress through the Akt\/Nrf2\/HO-1 signaling pathway","volume":"37","author":"Lu","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.4049\/jimmunol.176.3.1402","article-title":"CD40 expression by microglial cells is required for their completion of a two-step activation process during central nervous system autoimmune inflammation","volume":"176","author":"Ponomarev","year":"2006","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0165-5728(99)00053-3","article-title":"Activation of microglial cells by the CD40 pathway: Relevance to multiple sclerosis","volume":"97","author":"Tan","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Reddaway, J., Richardson, P.E., Bevan, R.J., Stoneman, J., and Palombo, M. (2023). Microglial morphometric analysis: So many options, so little consistency. Front. Neuroinform., 17.","DOI":"10.3389\/fninf.2023.1211188"},{"key":"ref_10","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. Neuroinflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1515\/jcim-2021-0251","article-title":"Phytochemistry and pharmacology of Celastrus paniculatus Wild.: A nootropic drug","volume":"20","author":"Aleem","year":"2021","journal-title":"J. Complement. Integr. Med."},{"key":"ref_12","first-page":"19","article-title":"An inside preview of nutritional and pharmacological profile of Celastrus paniculatus","volume":"1","author":"Katekhaye","year":"2011","journal-title":"Int. J. Recent Adv. Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3892\/br.2024.1734","article-title":"Celastrus paniculatus seed extract exhibits neuroprotective effects against MPP+ induced apoptotic cell death via GSK-3\u03b2 in a Parkinson\u2019s disease model","volume":"20","author":"Phattanakiatsakul","year":"2024","journal-title":"Biomed. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.phymed.2003.11.011","article-title":"Celastrus paniculatus seed oil and organic extracts attenuate hydrogen peroxide- and glutamate-induced injury in embryonic rat forebrain neuronal cells","volume":"13","author":"Godkar","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1080\/13880209.2017.1285945","article-title":"Ameliorating effect of Celastrus paniculatus standardized extract and its fractions on 3-nitropropionic acid induced neuronal damage in rats: Possible antioxidant mechanism","volume":"55","author":"Malik","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Matejuk, A., and Ransohoff, R.M. (2020). Crosstalk between astrocytes and microglia: An overview. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01416"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Quincozes-Santos, A., Bobermin, L.D., Latini, A., Wajner, M., Souza, D.O., Gon\u00e7alves, C.A., and Gottfried, C. (2013). Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064372"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2013.05.035","article-title":"Enhancement of FGF-1 release along with cytosolic proteins from rat astrocytes by hydrogen peroxide","volume":"1522","author":"Ito","year":"2013","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2015.04.008","article-title":"Biochemical properties in membrane of rat astrocytes under oxidative stress","volume":"1615","author":"Ito","year":"2015","journal-title":"Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/(SICI)1097-4547(19991115)58:4<576::AID-JNR10>3.0.CO;2-D","article-title":"Oxidative stress-induced metabolic alterations in rat brain astrocytes studied by multinuclear NMR spectroscopy","volume":"58","author":"Brand","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ihnatovych, I., Birkaya, B., Notari, E., and Szigeti, K. (2020). iPSC-derived microglia for modeling human-specific DAMP and PAMP responses in the context of Alzheimer\u2019s disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249668"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.humimm.2018.08.007","article-title":"IL-8 analogue CXCL8 (3-72) K11R\/G31P modulates LPS-induced inflammation via AKT1-NF-\u03baB and ERK1\/2-AP-1 pathways in THP-1 monocytes","volume":"79","author":"Walana","year":"2018","journal-title":"Hum. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s13311-016-0477-8","article-title":"Astrocytes: Integrative regulators of neuroinflammation in stroke and other neurological diseases","volume":"13","author":"Cekanaviciute","year":"2016","journal-title":"Neurotherapeutics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"697","DOI":"10.3233\/JAD-130131","article-title":"Omega-3 fatty acids enhance phagocytosis of Alzheimer\u2019s disease-related amyloid-\u03b242 by human microglia and decrease inflammatory markers","volume":"35","author":"Hjorth","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0197-4580(01)00246-9","article-title":"Identification of CD40 ligand in Alzheimer\u2019s disease and in animal models of Alzheimer\u2019s disease and brain injury","volume":"23","author":"Calingasan","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0006-8993(00)02984-X","article-title":"Expression of CD40 in the brain of Alzheimer\u2019s disease and other neurological diseases","volume":"885","author":"Togo","year":"2000","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1002\/ptr.7424","article-title":"An extensive review on phytochemistry and pharmacological activities of Indian medicinal plant Celastrus paniculatus Willd","volume":"36","author":"Nagpal","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1078\/0944-7113-00136","article-title":"Antioxidant property of Celastrus paniculatus Willd.: A possible mechanism in enhancing cognition","volume":"9","author":"Kumar","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mehla, J., Gupta, P., Pahuja, M., Diwan, D., and Diksha, D. (2020). Indian medicinal herbs and formulations for Alzheimer\u2019s disease, from traditional knowledge to scientific assessment. Brain Sci., 10.","DOI":"10.3390\/brainsci10120964"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5390307","DOI":"10.1155\/tswj\/5390307","article-title":"Enhancement of memory and synaptic plasticity by Celastrus paniculatus seed extract: Upregulation of pSer831-GluA1 trafficking and Arc\/PSD-95 expression in the hippocampus of male rats","volume":"2026","author":"Thongon","year":"2026","journal-title":"Sci. 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