{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T22:16:30Z","timestamp":1788041790327,"version":"build-2784847793"},"reference-count":48,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["RS-2024-00351313"],"award-info":[{"award-number":["RS-2024-00351313"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["RS-2023-00261934"],"award-info":[{"award-number":["RS-2023-00261934"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2021R1I1A2053285"],"award-info":[{"award-number":["2021R1I1A2053285"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["RS-2023-00248483"],"award-info":[{"award-number":["RS-2023-00248483"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Neurodegenerative disorders have emerged as a major global public health concern, and the burden is predicted to increase over time. Modulating neuroinflammation and microglial activity is considered a promising target for improving neurodegenerative disorders. The leaf of honeysuckle (LH), which has anti-inflammatory properties, has long been collected, regardless of the season, and used for medicinal purposes. However, research on its effects on neuroinflammation is scarce. In this study, we determined the neuroprotective effects of LH water extract by inhibiting microglial activation induced by lipopolysaccharide (LPS). Methods: The production or secretion of pro-inflammatory mediators was examined in LPS-exposed BV2 cells to ascertain the efficacy of LH water extract in improving neuroinflammation. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs) and the degradation of inhibitory \u03baB\u03b1 (I\u03baB\u03b1) were analyzed to elucidate the regulatory mechanisms of LH water extract. Ultra-performance liquid chromatography (UPLC) analysis was conducted to identify the active component of the LH. Results: LH water extract suppressed the formation of inducible nitric oxide synthase (iNOS), nitric oxide (NO), and pro-inflammatory cytokines, including interleukin (IL)-1\u03b2 and tumor necrosis factor (TNF)-\u03b1, in LPS-activated BV2 cells. LH impeded the activation of c-Jun N-terminal kinase (JNK). Moreover, chlorogenic acid was found in LH. Conclusions: The above findings suggest that LH water extract could improve neuroinflammation.<\/jats:p>","DOI":"10.3390\/nu16223954","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T11:58:07Z","timestamp":1732017487000},"page":"3954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Inflammatory Effects of Honeysuckle Leaf Against Lipopolysaccharide-Induced Neuroinflammation on BV2 Microglia"],"prefix":"10.3390","volume":"16","author":[{"given":"Bitna","family":"Kweon","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"},{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyoung","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"},{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yebin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongran","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donggu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dong-Eui University, 176 Eomgwang-ro, Busan 47340, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1288-0004","authenticated-orcid":false,"given":"Mikyung","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donguk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"},{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisang","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"},{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"},{"name":"Research Center of Traditional Korean Medicine, Wonkwang University, 460 Iksan-daero, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1474-4422(19)30411-9","article-title":"The global burden of neurological disorders: Translating evidence into policy","volume":"19","author":"Feigin","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"950","DOI":"10.14336\/AD.2021.0530","article-title":"Neurological and Neurodegenerative Disorders: Novel Concepts and Treatment","volume":"12","author":"Kirmani","year":"2021","journal-title":"Aging Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/ana.24897","article-title":"The burden of neurological disease in the United States: A summary report and call to action","volume":"81","author":"Gooch","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00702-009-0240-y","article-title":"Recent advances in our understanding of neurodegeneration","volume":"116","author":"Jellinger","year":"2009","journal-title":"J. Neural Transm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1582-4934.2010.01010.x","article-title":"Basic mechanisms of neurodegeneration: A critical update","volume":"14","author":"Jellinger","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_6","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_7","unstructured":"Kwon, D.-Y., Oh, M.-S., Bu, Y.-M., Seo, B.-I., Choi, H.-Y., and Lee, J.-H. (2012). Herbology, Younglimsa."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1134\/S1061934814080036","article-title":"Comparative investigation on chemical constituents of flower bud, stem and leaf of Lonicera japonica Thunb. by HPLC-DAD-ESI-MS\/MS n and GC-MS","volume":"69","author":"Ye","year":"2014","journal-title":"J. Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e31722","DOI":"10.1016\/j.heliyon.2024.e31722","article-title":"Comparative Study on Chemical Constituents of Different Medicinal Parts of Lonicera japonica Thunb. Based on LC-MS Combined with Multivariate Statistical Analysis","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/jsfa.10056","article-title":"Comparison of chemical constitution and bioactivity among different parts of Lonicera japonica Thunb","volume":"100","author":"Li","year":"2020","journal-title":"J. Sci. Food Agric."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00011-013-0674-4","article-title":"Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells","volume":"63","author":"Hwang","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_12","first-page":"481","article-title":"Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase, TNF-\u03b1, IL-1\u03b2 and COX-2 Expression by Flower and Whole Plant of Lonicera japonica","volume":"19","author":"Lee","year":"2005","journal-title":"J. Physiol. Pathol. Korean Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1089\/jmf.2014.3341","article-title":"Lonicera japonica THUNB. Extract Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses by Suppressing NF-\u03ba B Signaling in BV-2 Microglial Cells","volume":"18","author":"Kwon","year":"2015","journal-title":"J. Med. Food"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"811","DOI":"10.21037\/atm.2019.12.64","article-title":"The protective effect of Lonicera japonica polysaccharide on mice with depression by inhibiting NLRP3 inflammasome","volume":"7","author":"Liu","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1002\/ijc.23161","article-title":"Targeting NOX, INOS and COX-2 in inflammatory cells: Chemoprevention using food phytochemicals","volume":"121","author":"Murakami","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1089\/ars.2006.8.929","article-title":"Regulation of inducible nitric oxide synthase gene in glial cells","volume":"8","author":"Saha","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainresbull.2011.10.004","article-title":"Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases","volume":"87","author":"Smith","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4167\/jbv.2012.42.3.189","article-title":"Mitogen-activated protein kinases in inflammation","volume":"42","author":"Manzoor","year":"2012","journal-title":"J. Bacteriol. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mayne, K., White, J.A., McMurran, C.E., Rivera, F.J., and de la Fuente, A.G. (2020). Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.572090"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shao, F., Wang, X., Wu, H., Wu, Q., and Zhang, J. (2022). Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.825086"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, C.Y., Wang, X., Liu, C., and Zhang, H.L. (2019). Pharmacological Targeting of Microglial Activation: New Therapeutic Approach. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00514"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1523\/JNEUROSCI.1136-17.2017","article-title":"Microglia-Mediated Synapse Loss in Alzheimer\u2019s Disease","volume":"38","author":"Rajendran","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.immuni.2019.03.016","article-title":"Immune Signaling in Neurodegeneration","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Iova, O.-M., Marin, G.-E., Lazar, I., Stanescu, I., Dogaru, G., Nicula, C.A., and Bulboac\u0103, A.E. (2023). Nitric oxide\/nitric oxide synthase system in the pathogenesis of neurodegenerative disorders\u2014An overview. Antioxidants, 12.","DOI":"10.3390\/antiox12030753"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pneurobio.2005.06.001","article-title":"The physiology and pathophysiology of nitric oxide in the brain","volume":"76","author":"Guix","year":"2005","journal-title":"Progress Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12079-021-00663-x","article-title":"The modulation of neuroinflammation by inducible nitric oxide synthase","volume":"16","author":"Justo","year":"2022","journal-title":"J. Cell Commun. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yuste, J.E., Tarragon, E., Campuzano, C.M., and Ros-Bernal, F. (2015). Implications of glial nitric oxide in neurodegenerative diseases. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00322"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1177\/1535370221997052","article-title":"Nitric oxide modulation in neuroinflammation and the role of mesenchymal stem cells","volume":"246","author":"Liy","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1523\/JNEUROSCI.21-17-06480.2001","article-title":"Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity","volume":"21","author":"Brown","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/glia.10161","article-title":"Microglia as a source and target of cytokines","volume":"40","author":"Hanisch","year":"2002","journal-title":"Glia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100149","DOI":"10.1016\/j.crphar.2022.100149","article-title":"Role of pro-inflammatory cytokines in Alzheimer\u2019s disease and neuroprotective effects of pegylated self-assembled nanoscaffolds","volume":"4","author":"Rani","year":"2023","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/jnen\/59.6.471","article-title":"Interleukin-1 and the immunogenetics of Alzheimer disease","volume":"59","author":"Mrak","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00702-017-1732-9","article-title":"The IL-1beta phenomena in neuroinflammatory diseases","volume":"125","author":"Mendiola","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gonzalez Caldito, N. (2023). Role of tumor necrosis factor-alpha in the central nervous system: A focus on autoimmune disorders. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1213448"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Subedi, L., Lee, S.E., Madiha, S., Gaire, B.P., Jin, M., Yumnam, S., and Kim, S.Y. (2020). Phytochemicals against TNF \u03b1-mediated neuroinflammatory diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030764"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6703","DOI":"10.1021\/jf3007008","article-title":"Mitigation of inflammation with foods","volume":"60","author":"Wu","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1002\/ar.21047","article-title":"MAPK signal transduction underlying brain inflammation and gliosis as therapeutic target","volume":"292","author":"Kaminska","year":"2009","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104580","DOI":"10.1016\/j.psyneuen.2019.104580","article-title":"Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation","volume":"113","author":"Zhang","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"ra98","DOI":"10.1126\/scisignal.aaf5132","article-title":"Quantitative phosphoproteomic analysis identifies the critical role of JNK1 in neuroinflammation induced by Japanese encephalitis virus","volume":"9","author":"Ye","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Anfinogenova, N.D., Quinn, M.T., Schepetkin, I.A., and Atochin, D.N. (2020). Alarmins and c-Jun N-Terminal Kinase (JNK) Signaling in Neuroinflammation. Cells, 9.","DOI":"10.3390\/cells9112350"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, D., Du, N., Wen, L., Zhu, H., Liu, F., Wang, X., Du, J., and Li, S. (2017). An Efficient Method for the Preparative Isolation and Purification of Flavonoid Glycosides and Caffeoylquinic Acid Derivatives from Leaves of Lonicera japonica Thunb. Using High Speed Counter-Current Chromatography (HSCCC) and Prep-HPLC Guided by DPPH-HPLC Experiments. Molecules, 22.","DOI":"10.3390\/molecules22020229"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xiong, S., Su, X., Kang, Y., Si, J., Wang, L., Li, X., and Ma, K. (2023). Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1178188"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/agm2.12243","article-title":"Neurodegenerative disorders: Assessing the impact of natural vs drug-induced treatment options","volume":"6","author":"Mathur","year":"2023","journal-title":"Aging Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"884","DOI":"10.3390\/cimb46010056","article-title":"Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells","volume":"46","author":"Cho","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100675","DOI":"10.1016\/j.fochx.2023.100675","article-title":"Effect of honeysuckle leaf extract on the physicochemical properties of carboxymethyl konjac glucomannan\/konjac glucomannan\/gelatin composite edible film","volume":"18","author":"Wang","year":"2023","journal-title":"Food Chem. 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