{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:56Z","timestamp":1787028476650,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T00:00:00Z","timestamp":1648944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A1A03015642"],"award-info":[{"award-number":["2017R1A6A1A03015642"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Loratadine is an anti-histamine routinely used for treating allergies. However, recent findings have shown that Loratadine may also have anti-inflammatory functions, while their exact mechanisms have not yet been fully uncovered. In this paper, we investigated whether Loratadine can be utilized as an anti-inflammatory drug through a series of in vitro and in vivo experiments using a murine macrophage cell line and an acute gastritis mouse model. Loratadine was found to dramatically reduce the expression of pro-inflammatory genes, including MMP1, MMP3, and MMP9, and inhibit AP-1 transcriptional activation, as demonstrated by the luciferase assay. Therefore, we decided to further explore its role in the AP-1 signaling pathway. The expression of c-Jun and c-Fos, AP-1 subunits, was repressed by Loratadine and, correspondingly, the expression of p-JNK, p-MKK7, and p-TAK1 was also inhibited. In addition, Loratadine was able to reduce gastric bleeding in acute gastritis-induced mice; Western blotting using the stomach samples showed reduced p-c-Fos protein levels. Loratadine was shown to effectively suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production.<\/jats:p>","DOI":"10.3390\/ijms23073986","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T06:04:01Z","timestamp":1648965841000},"page":"3986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Jiwon","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Triseptya","family":"Hunto","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-3698","authenticated-orcid":false,"given":"Ji Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa Pyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-9801","authenticated-orcid":false,"given":"Han Gyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":false,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1385\/IR:23:2-3:099","article-title":"Innate immunity and inflammation: A transcriptional paradigm","volume":"23","author":"Hawiger","year":"2001","journal-title":"Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.iy.01.040183.002003","article-title":"Mediators of inflammation","volume":"1","author":"Larsen","year":"1983","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.3389\/fimmu.2018.02160","article-title":"Inflammation, a double-edge sword for cancer and other age-related diseases","volume":"9","author":"Gupta","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.cell.2015.02.010","article-title":"Homeostasis, inflammation, and disease susceptibility","volume":"160","author":"Kotas","year":"2015","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/cmi.2016.3","article-title":"Liver immunology and its role in inflammation and homeostasis","volume":"13","author":"Robinson","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jgr.2020.09.004","article-title":"Adaptogenic effects of Panax ginseng on modulation of immune functions","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1600-065X.2012.01146.x","article-title":"PAMPs and DAMPs: Signals that spur autophagy and immunity","volume":"249","author":"Tang","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-pathmechdis-012419-032847","article-title":"DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation","volume":"15","author":"Zindel","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jgr.2016.08.004","article-title":"Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases","volume":"41","author":"Kim","year":"2017","journal-title":"J. Ginseng Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jgr.2020.02.004","article-title":"Pharmacological potential of ginseng and its major component ginsenosides","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yang, W.S., Kim, H.G., Kim, E., Han, S.Y., Aziz, N., Yi, Y.-S., Kim, S., Lee, Y., Yoo, B.C., and Han, J.-W. (2020). Isoprenylcysteine carboxyl methyltransferase and its substrate Ras are critical players regulating TLR-mediated inflammatory responses. Cells, 9.","DOI":"10.3390\/cells9051216"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767366","DOI":"10.3389\/fimmu.2021.767366","article-title":"Syk-MyD88 axis Is a critical determinant of inflammatory-response in activated macrophages","volume":"12","author":"Kim","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1084\/jem.20031023","article-title":"LPS-TLR4 signaling to IRF-3\/7 and NF-\u03baB involves the Toll adapters TRAM and TRIF","volume":"198","author":"Fitzgerald","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jgr.2020.07.002","article-title":"Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis","volume":"45","author":"Xue","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ha, A.T., Rahmawati, L., You, L., Hossain, M.A., Kim, J.-H., and Cho, J.Y. (2021). Anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis effects of quercetin 3-O-\u03b2-D-glucuronide in human keratinocytes and melanoma cells via activation of NF-\u03baB and AP-1 pathways. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010433"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kim, E., Ahuja, A., Kim, M.-Y., and Cho, J.Y. (2021). DNA or protein methylation-dependent regulation of activator protein-1 function. Cells, 10.","DOI":"10.3390\/cells10020461"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"i109","DOI":"10.1136\/ard.2010.140533","article-title":"Targeting inflammation by modulating the Jun\/AP-1 pathway","volume":"70","author":"Schonthaler","year":"2011","journal-title":"Ann. Rheum."},{"key":"ref_21","first-page":"5484","article-title":"LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-\u03baB, STAT3 or AP-1 activation","volume":"17","author":"Liu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s001090050063","article-title":"Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways","volume":"74","author":"Whitmarsh","year":"1996","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1476-5586(03)80025-8","article-title":"The Role of JNK and p38 MAPK Activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression","volume":"5","author":"Silvers","year":"2003","journal-title":"Neoplasia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/jcb.20458","article-title":"Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-\u03b21 involves MAPK, Smad and AP-1 signalling pathways","volume":"95","author":"Davies","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36993","DOI":"10.1074\/jbc.M302942200","article-title":"Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1","volume":"278","author":"Morse","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/jcp.21041","article-title":"EGF-R regulates MMP function in fibroblasts through MAPK and AP-1 pathways","volume":"212","author":"Kajanne","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1042\/bj20020707","article-title":"A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimers","volume":"369","author":"Bergman","year":"2003","journal-title":"Biochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1006\/cyto.2000.0743","article-title":"Integration of the NF-\u03baB and mitogen-activated protein kinase\/AP-1 pathways at the collagenase-1 promoter: Divergence of IL-1 and TNF-dependent signal transduction in rabbit primary synovial fibroblasts","volume":"12","author":"Barchowsky","year":"2000","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18649","DOI":"10.1074\/jbc.M111415200","article-title":"Cyclooxygenase-2 is overexpressed in HER-2\/neu-positive breast cancer: Evidence for involvement of AP-1 and PEA3","volume":"277","author":"Subbaramaiah","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/emm.2005.25","article-title":"Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets","volume":"37","author":"Cho","year":"2005","journal-title":"Exp. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/302832a0","article-title":"Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor","volume":"302","author":"Arrang","year":"1983","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/244287a0","article-title":"Inhibition of histamine release by histamine controlled by H2 receptor","volume":"244","author":"Lichtenstein","year":"1973","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3389\/fimmu.2018.01873","article-title":"The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: The hunt for new therapeutic targets","volume":"9","author":"Thangam","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9524075","DOI":"10.1155\/2018\/9524075","article-title":"Role of histamine in modulating the immune response and inflammation","volume":"2018","author":"Branco","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1398-9995.1987.tb02188.x","article-title":"Antiallergic activity of loratadine, a non-sedating antihistamine","volume":"42","author":"Kreutner","year":"1987","journal-title":"Allergy"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1365-2222.1999.0290s3147.x","article-title":"Loratadine: A non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation","volume":"29","author":"Kay","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/j.1365-2222.2008.02990.x","article-title":"Histamine H1-receptor antagonists inhibit nuclear factor-kappaB and activator protein-1 activities via H1-receptor-dependent and-independent mechanisms","volume":"38","author":"Roumestan","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000096016","article-title":"New evidence of H1-receptor independent COX-2 inhibition by fexofenadine HCl in vitro","volume":"78","author":"Juergens","year":"2006","journal-title":"Pharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.biopha.2018.07.025","article-title":"Histamine H1 type receptor antagonist loratadine ameliorates oxidized LDL induced endothelial dysfunction","volume":"106","author":"Zhou","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.24193\/subbchem.2017.1.07","article-title":"Resveratrol and loratadine effects on oxidative stress induced by experimental inflammation","volume":"62","author":"Mitrea","year":"2017","journal-title":"Studia UBB Chemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1159\/000093709","article-title":"Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: Implications for anti-inflammatory activity of antihistamines","volume":"140","author":"Ring","year":"2006","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113949","DOI":"10.1016\/j.bcp.2020.113949","article-title":"Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway","volume":"177","author":"Hunto","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0945-053X(97)90026-3","article-title":"The AP-1 site and MMP gene regulation: What is all the fuss about?","volume":"15","author":"Benbow","year":"1997","journal-title":"Matrix Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0945-053X(02)00007-0","article-title":"Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-\u03baB) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes","volume":"21","author":"Liacini","year":"2002","journal-title":"Matrix Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0925-4439(97)00068-9","article-title":"Suppression of NF-\u03baB and AP-1 activation by glucocorticoids in experimental glomerulonephritis in rats: Molecular mechanisms of anti-nephritic action","volume":"1362","author":"Sakurai","year":"1997","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_46","first-page":"129","article-title":"The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation","volume":"1072","author":"Angel","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Boby, N., Abbas, M.A., Lee, E.-B., Im, Z.-E., Hsu, W.H., and Park, S.-C. (2021). Protective effect of Pyrus ussuriensis Maxim. extract against ethanol-induced gastritis in rats. Antioxidants, 10.","DOI":"10.3390\/antiox10030439"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1007\/BF02071395","article-title":"Reversion by histamine H2-receptor antagonists of plasma membrane alterations in ethanol-induced gastritis","volume":"41","year":"1996","journal-title":"Am. J. Dig. Dis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3746\/pnf.2020.25.2.158","article-title":"Gastroprotective effects of Cudrania tricuspidata leaf extracts by suppressing gastric cAMP and increasing gastric mucins","volume":"25","author":"Kim","year":"2020","journal-title":"Prev. Nutr. Food Sci."},{"key":"ref_50","first-page":"464P","article-title":"Ranitidine (AH 19065): A new potent, selective histamine H2-receptor antagonist [proceedings]","volume":"66","author":"Bradshaw","year":"1979","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1056\/NEJM198312013092206","article-title":"Ranitidine: A new H2-receptor antagonist","volume":"309","author":"Zeldis","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1038\/sj.onc.1210413","article-title":"Ubiquitin-mediated activation of TAK1 and IKK","volume":"26","author":"Adhikari","year":"2007","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S0014-5793(00)01146-7","article-title":"TAK1 mediates an activation signal from toll-like receptor (s) to nuclear factor-\u03baB in lipopolysaccharide-stimulated macrophages","volume":"467","author":"Irie","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jmb.2005.09.098","article-title":"Structural basis for the interaction of TAK1 kinase with its activating protein TAB1","volume":"354","author":"Brown","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1038\/ni1255","article-title":"Essential function for the kinase TAK1 in innate and adaptive immune responses","volume":"6","author":"Sato","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: Regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0092-8674(00)81110-1","article-title":"Genetic analysis of autoimmune disease","volume":"85","author":"Vyse","year":"1996","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/bjs.1800840707","article-title":"Systemic inflammatory response syndrome","volume":"84","author":"Davies","year":"1997","journal-title":"J. Br. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1038\/ncb0502-e131","article-title":"AP-1 as a regulator of cell life and death","volume":"4","author":"Shaulian","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1038\/sj.onc.1204383","article-title":"AP-1 in cell proliferation and survival","volume":"20","author":"Shaulian","year":"2001","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1242\/jcs.01589","article-title":"AP-1 subunits: Quarrel and harmony among siblings","volume":"117","author":"Hess","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/B:BREA.0000032982.49024.71","article-title":"The role of the AP-1 transcription factors c-Fos, FosB, Fra-1 and Fra-2 in the invasion process of mammary carcinomas","volume":"86","author":"Andritzky","year":"2004","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.bbrc.2004.04.055","article-title":"Dual actions of nitric oxide on angiogenesis: Possible roles of PKC, ERK, and AP-1","volume":"318","author":"Jones","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0092-8674(88)90076-1","article-title":"The c-fos protein interacts with c-JunAP-1 to stimulate transcription of AP-1 responsive genes","volume":"54","author":"Chiu","year":"1988","journal-title":"Cell"},{"key":"ref_65","first-page":"685","article-title":"AP-1 (Fos\/Jun) transcription factors in hematopoietic differentiation and apoptosis","volume":"12","author":"Liebermann","year":"1998","journal-title":"Int. J. Oncol."},{"key":"ref_66","first-page":"1505","article-title":"Fermented Noni exudate (fNE): A mediator between immune system and anti-tumor activity","volume":"20","author":"Li","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/sj.bjp.0705345","article-title":"Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells","volume":"139","author":"Oltmanns","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1053\/jhep.2003.50135","article-title":"c-Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration","volume":"37","author":"Schwabe","year":"2003","journal-title":"Hepatology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1093\/emboj\/20.13.3459","article-title":"Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1","volume":"20","author":"Wulf","year":"2001","journal-title":"EMBO J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0092-8674(03)00042-4","article-title":"Liver tumor development: C-Jun antagonizes the proapoptotic activity of p53","volume":"112","author":"Eferl","year":"2003","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1101\/gad.390506","article-title":"c-Jun\/AP-1 controls liver regeneration by repressing p53\/p21 and p38 MAPK activity","volume":"20","author":"Stepniak","year":"2006","journal-title":"Genes Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s10571-014-0132-z","article-title":"Up-regulation of c-Fos associated with neuronal apoptosis following intracerebral hemorrhage","volume":"35","author":"Chen","year":"2015","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10352","DOI":"10.1128\/MCB.24.23.10352-10365.2004","article-title":"Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas\/FasL and tumor necrosis factor (TNF) receptor 1\/TNF-\u03b1 expression","volume":"24","author":"Wang","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22414","DOI":"10.1074\/jbc.M110.120121","article-title":"Protein kinase C isoforms \u03b6 and \u03b9 mediate collagenase expression and cartilage destruction via STAT3- and ERK-dependent c-fos induction","volume":"285","author":"Litherland","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16983","DOI":"10.1038\/s41598-017-17289-y","article-title":"A selective inhibition of c-Fos\/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain","volume":"7","author":"Makino","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/jop.12296","article-title":"Overexpression of c-fos promotes cell invasion and migration via CD44 pathway in oral squamous cell carcinoma","volume":"44","author":"Dong","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1128\/MCB.17.2.963","article-title":"AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44","volume":"17","author":"Lamb","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.bbrc.2018.02.147","article-title":"A selective c-Fos\/AP-1 inhibitor prevents cartilage destruction and subsequent osteophyte formation","volume":"497","author":"Motomura","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nbt1412","article-title":"Treatment of arthritis with a selective inhibitor of c-Fos\/activator protein-1","volume":"26","author":"Aikawa","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.chembiol.2017.07.011","article-title":"Takinib, a selective TAK1 inhibitor, broadens the therapeutic efficacy of TNF-\u03b1 inhibition for cancer and autoimmune disease","volume":"24","author":"Totzke","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13075-019-2073-x","article-title":"Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice","volume":"21","author":"Scarneo","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00280-015-2822-8","article-title":"Inhibition of ovarian cancer cell growth by a novel TAK1 inhibitor LYTAK1","volume":"76","author":"Ying","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33666","DOI":"10.18632\/oncotarget.16895","article-title":"TAK1 inhibitor 5Z-7-oxozeaenol sensitizes cervical cancer to doxorubicin-induced apoptosis","volume":"8","author":"Guan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/cb3005897","article-title":"Mechanism and in vitro pharmacology of TAK1 inhibition by (5Z)-7-oxozeaenol","volume":"8","author":"Wu","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1007\/s10495-013-0864-0","article-title":"TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy","volume":"18","author":"Fan","year":"2013","journal-title":"Apoptosis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jgr.2020.12.003","article-title":"Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes","volume":"45","author":"Lee","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Jang, J., Lee, J.S., Jang, Y.-J., Choung, E.S., Li, W.Y., Lee, S.W., Kim, E., Kim, J.-H., and Cho, J.Y. (2020). Sorbaria kirilowii ethanol extract exerts anti-inflammatory effects in vitro and in vivo by targeting Src\/nuclear factor (NF)-\u03baB. Biomolecules, 10.","DOI":"10.3390\/biom10050741"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/mnfr.201400820","article-title":"Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain","volume":"59","author":"Kim","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jgr.2019.11.001","article-title":"Gastroprotective effects of the nonsaponin fraction of Korean Red Ginseng through cyclooxygenase-1 upregulation","volume":"44","author":"Lee","year":"2020","journal-title":"J. Ginseng Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"113797","DOI":"10.1016\/j.bcp.2020.113797","article-title":"The kinase inhibitor BX795 suppresses the inflammatory response via multiple kinases","volume":"174","author":"Yu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Song, C., Lorz, L.R., Lee, J., and Cho, J.Y. (2021). In vitro photoprotective, anti-inflammatory, moisturizing, and antimelanogenic effects of a methanolic extract of Chrysophyllum lucentifolium Cronquist. Plants, 11.","DOI":"10.3390\/plants11010094"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ahuja, A., Kim, M.-Y., and Cho, J.Y. (2019). Protium javanicum Burm. methanol extract attenuates LPS-induced inflammatory activities in macrophage-like RAW264.7 cells. Evidence-Based Complement. Altern. Med., 2019.","DOI":"10.1155\/2019\/2910278"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112161","DOI":"10.1016\/j.jep.2019.112161","article-title":"Viburnum pichinchense methanol extract exerts anti-inflammatory effects via targeting the NF-\u03baB and caspase-11 non-canonical inflammasome pathways in macrophages","volume":"245","author":"Hwang","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Aziz, N., Hong, Y.H., Jo, M.K., Kim, J.K., Kim, K.-H., Ashktorab, H., Smoot, D.T., Hur, H., Yoo, B.C., and Cho, J.Y. (2020). Molecular signatures of JMJD10\/MINA53 in gastric cancer. Cancers, 12.","DOI":"10.3390\/cancers12051141"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"113887","DOI":"10.1016\/j.jep.2021.113887","article-title":"Syk\/NF-\u03baB-targeted anti-inflammatory activity of Melicope accedens (Blume) TG Hartley methanol extract","volume":"271","author":"Kim","year":"2021","journal-title":"J. Ethnopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3986\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:49:18Z","timestamp":1760136558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,3]]},"references-count":95,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073986"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073986","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,3]]}}}