{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:48:34Z","timestamp":1791920914581,"version":"4.3.4"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Program of Shanxi Province","award":["20210302123328"],"award-info":[{"award-number":["20210302123328"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["2020L0236"],"award-info":[{"award-number":["2020L0236"]}]},{"name":"Fundamental Research Program of Shanxi Province","award":["42071067"],"award-info":[{"award-number":["42071067"]}]},{"name":"Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi","award":["20210302123328"],"award-info":[{"award-number":["20210302123328"]}]},{"name":"Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi","award":["2020L0236"],"award-info":[{"award-number":["2020L0236"]}]},{"name":"Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi","award":["42071067"],"award-info":[{"award-number":["42071067"]}]},{"name":"National Natural Science Foundation of China","award":["20210302123328"],"award-info":[{"award-number":["20210302123328"]}]},{"name":"National Natural Science Foundation of China","award":["2020L0236"],"award-info":[{"award-number":["2020L0236"]}]},{"name":"National Natural Science Foundation of China","award":["42071067"],"award-info":[{"award-number":["42071067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The leaves of Rhamnus erythroxylon Pall. are widely used as tea substitutes in northwest China for their fragrant aroma, anti-irritability, and digestion-enhancing properties. Ombuin, a main flavonoid compound found in the leaves, exhibited notable anti-inflammatory and antioxidant effects. However, its potential role in treating neuroinflammatory-related diseases remains unexplored. Thus, this study aims to evaluate the anti-neuroinflammatory effects of ombuin and to explore the underlying molecular mechanisms. According to our findings, ombuin dramatically reduced the release of interleukin-6 (IL-6), tumor necrosis factor-\u03b1 (TNF-\u03b1), IL-1\u03b2, nitric oxide (NO), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further analysis, including transcriptomics, network pharmacology, molecular docking, and cellular heat transfer assays, revealed that Src was a direct target of ombuin. Western blot analysis showed that ombuin effectively suppressed Src phosphorylation and inhibited the downstream expressions of p-PI3K p85, p-AKT1, p-IKK\u03b1\/\u03b2, p-I\u03baB\u03b1, and nuclear factor \u03baB (NF-\u03baB). Meanwhile, the repression of Src significantly reversed the anti-neuroinflammatory activity of ombuin. Our results identified Src as a direct target of ombuin and implied that ombuin exerted an anti-neuroinflammatory effect by inhibiting Src phosphorylation and suppressing the activation of the PI3K-AKT and NF-\u03baB pathways, which might provide an alternative therapeutic strategy for neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms25168789","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Anti-Neuroinflammatory Effect of Ombuin from Rhamnus\u00a0erythroxylon Pall. Leaves in LPS-Induced BV-2 Microglia by Targeting Src and Suppressing the PI3K-AKT\/NF-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"25","author":[{"given":"Yanjie","family":"Bian","sequence":"first","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Qiao","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyun","family":"Han","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixiang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuofu","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Life Science, Shanxi Normal University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","unstructured":"Maher, P. (2019). The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123056"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153164","DOI":"10.1016\/j.phymed.2019.153164","article-title":"Centipeda minima extract exerts antineuroinflammatory effects via the inhibition of NF-\u03baB signaling pathway","volume":"67","author":"Li","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Decandia, D., Gelfo, F., Landolfo, E., Balsamo, F., Petrosini, L., and Cutuli, D. (2023). Dietary Protection against Cognitive Impairment, Neuroinflammation and Oxidative Stress in Alzheimer\u2019s Disease Animal Models of Lipopolysaccharide-Induced Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065921"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s12974-023-02919-2","article-title":"Human iPSC-derived glia models for the study of neuroinflammation","volume":"20","author":"Maguire","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Muzio, L., Viotti, A., and Martino, G. (2021). Microglia in neuroinflammation and neurodegeneration: From understanding to therapy. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.742065"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s12640-020-00197-x","article-title":"Hispidulin Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia and Attenuates the Activation of Akt, NF-\u03baB, and STAT3 Pathway","volume":"38","author":"Yu","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ismail, E.N., Jantan, I., Vidyadaran, S., Jamal, J.A., and Azmi, N. (2020). Phyllanthus amarus prevents LPS-mediated BV2 microglial activation via MyD88 and NF-\u03baB signaling pathways. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-02961-0"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.4049\/jimmunol.179.6.4142","article-title":"Involvement of phosphatidylinositol 3-kinase-mediated up-regulation of I kappa B alpha in anti-inflammatory effect of gemfibrozil in microglia","volume":"179","author":"Jana","year":"2007","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.jpha.2023.09.012","article-title":"Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease: A systematic review","volume":"13","author":"Gandhi","year":"2023","journal-title":"J. Pharm. Anal."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xu, G., Dong, F., Su, L., Tan, Z.X., Lei, M., Li, L., Wen, D., and Zhang, F. (2024). The role and therapeutic potential of nuclear factor \u03baB (NF-\u03baB) in ischemic stroke. Biomed. Pharmacother., 171.","DOI":"10.1016\/j.biopha.2024.116140"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.fct.2018.09.005","article-title":"Role of protein kinase C\u03b4 in dopaminergic neurotoxic events","volume":"121","author":"Shin","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1007\/s11064-017-2301-1","article-title":"Matairesinol Suppresses Neuroinflammation and Migration Associated with Src and ERK1\/2-NF-\u03baB Pathway in Activating BV2 Microglia","volume":"42","author":"Xu","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, C.C., Lin, C.C., Hsiao, L.D., Kuo, J.M., Tseng, H.C., and Yang, C.M. (2020). Lipopolysaccharide-Induced Matrix Metalloproteinase-9 Expression Associated with Cell Migration in Rat Brain Astrocytes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010259"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.molimm.2004.04.010","article-title":"Src-family kinases: Rheostats of immune cell signaling","volume":"41","author":"Lowell","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gage, M., Putra, M., Wachter, L., Dishman, K., Gard, M., Gomez-Estrada, C., and Thippeswamy, T. (2022). Saracatinib, a Src Tyrosine Kinase Inhibitor, as a Disease Modifier in the Rat DFP Model: Sex Differences, Neurobehavior, Gliosis, Neurodegeneration, and Nitro-Oxidative Stress. Antioxidants, 11.","DOI":"10.3390\/antiox11010061"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuropharm.2013.07.020","article-title":"Inhibition of Src tyrosine kinase activity by squamosamide derivative FLZ attenuates neuroinflammation in both in vivo and in vitro Parkinson\u2019s disease models","volume":"75","author":"Tai","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bosco, F., Ruga, S., Citraro, R., Leo, A., Guarnieri, L., Maiuolo, J., Oppedisano, F., Macr\u00ec, R., Scarano, F., and Nucera, S. (2023). The Effects of Andrographis paniculata (Burm.F.) Wall. Ex Nees and Andrographolide on Neuroinflammation in the Treatment of Neurodegenerative Diseases. Nutrients, 15.","DOI":"10.3390\/nu15153428"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Barber, K., Mendonca, P., Evans, J.A., and Soliman, K.F.A. (2023). Antioxidant and Anti-Inflammatory Mechanisms of Cardamonin through Nrf2 Activation and NF-kB Suppression in LPS-Activated BV-2 Microglial Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310872"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Elbandy, M. (2023). Anti-Inflammatory Effects of Marine Bioactive Compounds and Their Potential as Functional Food Ingredients in the Prevention and Treatment of Neuroinflammatory Disorders. Molecules, 28.","DOI":"10.3390\/molecules28010002"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.lfs.2005.07.029","article-title":"Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits","volume":"78","author":"Alhamdani","year":"2006","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T., Ketha, A., Hieu, H.V., and Tatipamula, V.B. (2021). In vitro antimycobacterial studies of flavonols from Bauhinia vahlii Wight and Arn. 3 Biotech, 11.","DOI":"10.1007\/s13205-021-02672-4"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/ptr.2448","article-title":"Antiinflammatory activities of flavonoids and a triterpene caffeate isolated from Bauhinia variegata","volume":"22","author":"Rao","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2018.10.018","article-title":"Standardization and xanthine oxidase inhibitory potential of Zanthoxylum armatum fruits","volume":"230","author":"Ranjana","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1007\/s11427-013-4557-2","article-title":"Transcriptomics: Advances and approaches","volume":"56","author":"Dong","year":"2013","journal-title":"Sci. China Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-2094-1-14","article-title":"Microglia and neuroinflammation: A pathological perspective","volume":"1","author":"Streit","year":"2004","journal-title":"J. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.intimp.2018.06.016","article-title":"Formononetin inhibits neuroinflammation and increases estrogen receptor beta (ER\u03b2) protein expression in BV2 microglia","volume":"61","author":"Olajide","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jphs.2018.02.004","article-title":"Neurotropin inhibits neuroinflammation via suppressing NF-\u03baB and MAPKs signaling pathways in lipopolysaccharide-stimulated BV2 cells","volume":"136","author":"Zheng","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.biocel.2010.07.005","article-title":"Microglia: Activation in acute and chronic inflammatory states and in response to cardiovascular dysfunction","volume":"42","author":"Badoer","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_32","first-page":"27","article-title":"Herbal versus synthetic drugs; beliefs and facts","volume":"4","author":"Karimi","year":"2015","journal-title":"J. Nephropharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"So, Y.J., Lee, J.U., Yang, G.S., Yang, G., Kim, S.W., Lee, J.H., and Kim, J.U. (2024). The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson\u2019s Disease: A Promising Therapeutic Approach. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021071"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, W., Xu, H., Li, C., Han, B., and Zhang, Y. (2024). Exploring Chinese herbal medicine for ischemic stroke: Insights into microglia and signaling pathways. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1333006"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ross, F.C., Mayer, D.E., Horn, J., Cryan, J.F., Del Rio, D., Randolph, E., Gill, C.I.R., Gupta, A., Ross, R.P., and Stanton, C. (2024). Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: A role for gut microbiota?. Nutr. Neurosci., 1\u201319.","DOI":"10.1080\/1028415X.2023.2298098"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"He, Y.Q., Zhou, C.C., Jiang, S.G., Lan, W.Q., Zhang, F., Tao, X., and Chen, W.S. (2024). Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1292807"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dias, M.C., Pinto, D.C.G.A., and Silva, A.M.S. (2021). Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules, 26.","DOI":"10.3390\/molecules26175377"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Cianciulli, A., Porro, C., Calvello, R., Trotta, T., Lofrumento, D.D., and Panaro, M.A. (2020). Microglia Mediated Neuroinflammation: Focus on PI3K Modulation. Biomolecules, 10.","DOI":"10.3390\/biom10010137"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Panneerselvan, P., Vasanthakumar, K., Muthuswamy, K., Krishnan, V., and Subramaniam, S. (2023). Insights on the functional dualism of nitric oxide in the hallmarks of cancer. Biochim. Biophys. Acta Rev. Cancer, 1878.","DOI":"10.1016\/j.bbcan.2023.189001"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Russell, T.M., and Richardson, D.R. (2023). The good Samaritan glutathione-S-transferase P1: An evolving relationship in nitric oxide metabolism mediated by the direct interactions between multiple effector molecules. Redox Biol., 59.","DOI":"10.1016\/j.redox.2022.102568"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.intimp.2013.11.020","article-title":"Downregulation of NO and PGE2 in LPS-stimulated BV2 microglial cells by trans-isoferulic acid via suppression of PI3K\/Akt-dependent NF-\u03baB and activation of Nrf2-mediated HO-1","volume":"18","author":"Dilshara","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s11481-014-9556-y","article-title":"\u03b2-Arrestin 2 mediates the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells","volume":"9","author":"Du","year":"2014","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.expneurol.2013.05.014","article-title":"A survey from 2012 of evidence for the role of neuroinflammation in neurotoxin animal models of Parkinson\u2019s disease and potential molecular targets","volume":"256","author":"Ramsey","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.neuropharm.2014.01.022","article-title":"Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1\/IKK\/NF-\u03baB, MAPKs and Akt signaling pathways","volume":"79","author":"Wang","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Akanchise, T., and Angelova, A. (2023). Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome. Antioxidants, 12.","DOI":"10.3390\/antiox12020393"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S357","DOI":"10.3233\/JAD-2010-100498","article-title":"Reactive oxygen species: Stuck in the middle of neurodegeneration","volume":"20","author":"Patten","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155374","DOI":"10.1016\/j.phymed.2024.155374","article-title":"Neuropharmacological insights into Gardenia jasminoides Ellis: Harnessing therapeutic potential for central nervous system disorders","volume":"125","author":"Hou","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112537","DOI":"10.1016\/j.jep.2019.112537","article-title":"Exploration the active compounds of Astragali Radix in treatment of adriamycin nephropathy by network pharmacology combined with transcriptomic approach","volume":"258","author":"Li","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sun, Q., Wang, H., Yang, M., Xia, H., Wu, Y., Liu, Q., and Tang, H. (2023). miR-153-3p via PIK3R1 Is Involved in Cigarette Smoke-Induced Neurotoxicity in the Brain. Toxics, 11.","DOI":"10.3390\/toxics11120969"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/1742-2094-9-178","article-title":"Inhibition of EGFR\/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury","volume":"9","author":"Qu","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1080\/01677063.2022.2114471","article-title":"PTK2 regulates tau-induced neurotoxicity via phosphorylation of p62 at Ser403","volume":"37","author":"Lee","year":"2023","journal-title":"J. Neurogenet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Cohen, J., Mathew, A., Dourvetakis, K.D., Sanchez-Guerrero, E., Pangeni, R.P., Gurusamy, N., Aenlle, K.K., Ravindran, G., Twahir, A., and Isler, D. (2024). Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders. Cells, 13.","DOI":"10.3390\/cells13060511"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.molimm.2009.10.012","article-title":"Src kinase participates in LPS-induced activation of NADPH oxidase","volume":"47","author":"Check","year":"2010","journal-title":"Mol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12974-014-0140-4","article-title":"Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K\/Akt\/FoxO1 pathway","volume":"11","author":"Dong","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47834","DOI":"10.1074\/jbc.M302660200","article-title":"Oxidative stress reprograms lipopolysaccharide signaling via Src kinase-dependent pathway in RAW 264.7 macrophage cell line","volume":"278","author":"Khadaroo","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1742-2094-9-117","article-title":"Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer\u2019s disease","volume":"9","author":"Dhawan","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12935-024-03357-7","article-title":"PI3K\/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells","volume":"24","author":"Moghbeli","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: New insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154899","DOI":"10.1016\/j.phymed.2023.154899","article-title":"Oxyberberine ameliorates TNBS-induced colitis in rats through suppressing inflammation and oxidative stress via Keap1\/Nrf2\/NF-\u03baB signaling pathways","volume":"116","author":"Li","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41467-020-14433-7","article-title":"Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase","volume":"11","author":"Palmieri","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Seo, S.Y., Joo, S.H., Lee, S.-O., Yoon, G., Cho, S.-S., Choi, Y.H., Park, J.W., and Shim, J.-H. (2024). Activation of p38 and JNK by ROS Contributes to Deoxybouvardin-Mediated Intrinsic Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells. Antioxidants, 13.","DOI":"10.3390\/antiox13070866"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.phymed.2016.10.007","article-title":"Anti-neuroinflammatory effect of Sophoraflavanone G from Sophora alopecuroides in LPS-activated BV2 microglia by MAPK, JAK\/STAT and Nrf2\/HO-1 signaling pathways","volume":"23","author":"Guo","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Peng, J.C., Deng, Y., Song, H.X., Fang, Y.Y., Gan, C.L., Lin, J.J., Luo, J.J., Zheng, X.W., Aschner, M., and Jiang, Y.M. (2023). Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells. Brain Sci., 13.","DOI":"10.3390\/brainsci13030382"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:35:41Z","timestamp":1760110541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168789"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168789","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]}}}