{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:00:38Z","timestamp":1789441238502,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"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":["No. 2019R1A2C2087608"],"award-info":[{"award-number":["No. 2019R1A2C2087608"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGS1002012"],"award-info":[{"award-number":["KGS1002012"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGS1172012"],"award-info":[{"award-number":["KGS1172012"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2) and interleukin-6 (IL-6) but not tumor necrosis factor \u03b1 (TNF-\u03b1). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-\u03baB). In a mouse model, oral administration of 50 mg\/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.<\/jats:p>","DOI":"10.3390\/molecules25153345","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T11:26:01Z","timestamp":1595503561000},"page":"3345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Acyclic Triterpenoid Isolated from Alpinia katsumadai Alleviates Formalin-Induced Chronic Mouse Paw Inflammation by Inhibiting the Phosphorylation of ERK and NF-\u03baB"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-6766","authenticated-orcid":false,"given":"Hyung Jin","family":"Lim","sequence":"first","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"},{"name":"Department of Bioactive Material Sciences, Chonbuk National University, Jeonju-si, Jeonbuk 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Gyeong","family":"Bak","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"},{"name":"Department of Marine Bio Food Science, Chonnam National University, Korea, Yeosu-si, Jeonnam 59626, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Ju","family":"Lim","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"},{"name":"Division of Biotechnology and Advanced Institute of Environment and Bioscience, Jeonbuk National University, Iksan-si, Jeonbuk 54596, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1025-7363","authenticated-orcid":false,"given":"Seung Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-6477","authenticated-orcid":false,"given":"Soyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-3804","authenticated-orcid":false,"given":"Sae-Kwang","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan-si, Gyeonbuk 38610, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Ik","family":"Park","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chonnam National University, Gwangju-si 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-7666","authenticated-orcid":false,"given":"Seung-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mun-Chual","family":"Rho","sequence":"additional","affiliation":[{"name":"Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen recognition and inflammatory signaling in innate immune defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1128\/MCB.24.17.7806-7819.2004","article-title":"NF-\u03baB and AP-1 connection: Mechanism of NF-\u03baB-dependent regulation of AP-1 activity","volume":"24","author":"Fujioka","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.molmed.2007.09.002","article-title":"Signaling to NF-\u03baB by Toll-like receptors","volume":"13","author":"Kawai","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1749-6632.2009.05301.x","article-title":"The role of proinflammatory cytokines in the generation and maintenance of joint pain","volume":"1193","author":"Schaible","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"d12","DOI":"10.2741\/A171","article-title":"Cytokines in acute and chronic inflammation","volume":"2","author":"Feghali","year":"1997","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1136\/gut.42.4.470","article-title":"Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation","volume":"42","author":"Nikolaus","year":"1998","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"d694","DOI":"10.2741\/Martel","article-title":"Cytokines and their role in the pathophysiology of osteoarthritis","volume":"4","author":"Alaaeddine","year":"1999","journal-title":"Front. Biosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1136\/thx.54.9.825","article-title":"Cytokines in asthma","volume":"54","author":"Chung","year":"1999","journal-title":"Thorax"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/BF00920636","article-title":"Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases","volume":"13","author":"Raziuddin","year":"1993","journal-title":"J. Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/ptr.1291","article-title":"Antioxidant activity of extracts from Alpinia katsumadai seed","volume":"17","author":"Lee","year":"2003","journal-title":"Phytotherapy Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1021\/np990096e","article-title":"Two novel anti-emetic principles of Alpinia katsumadai","volume":"62","author":"Yang","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.phytol.2017.09.009","article-title":"A constituent of Alpinia katsumadai suppresses allergic airway inflammation","volume":"22","author":"Wang","year":"2017","journal-title":"Phytochem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/ptr.2610","article-title":"Alpinia katsumadai hayata prevents mouse sepsis induced by cecal ligation and puncture through promoting bacterial clearance and downregulating systemic inflammation","volume":"23","author":"Yang","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jang, H.J., Lee, S.J., Lee, S., Jung, K., Lee, S.W., and Rho, M.C. (2017). Acyclic Triterpenoids from Alpinia katsumadai inhibit IL-6-induced STAT3 activation. Molecules, 22.","DOI":"10.3390\/molecules22101611"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1128\/mr.48.3.181-198.1984","article-title":"Bacterial triterpenoids","volume":"48","author":"Taylor","year":"1984","journal-title":"Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.proenv.2012.05.010","article-title":"Biosynthesis of isoprene units in the C34 botryococcene molecule produced by Botryococcus braunii strain Bot-22","volume":"15","author":"Ishimatsu","year":"2012","journal-title":"Procedia Environ. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1248\/bpb.b12-00617","article-title":"2, 3, 22, 23-Tetrahydroxyl-2, 6, 10, 15, 19, 23-hexamethyl-6, 10, 14, 18-tetracosatetraene, an acyclic triterpenoid isolated from the seeds of Alpinia katsumadai, Inhibits Acyl-CoA: Cholesterol Acyltransferase Activity","volume":"35","author":"Choi","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1021\/np0780093","article-title":"Antiplasmodial triterpenoids from Ekebergia capensis","volume":"71","author":"Murata","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Teixeira, E.W., Negri, G., Salatino, A., and Stringheta, P.C. (2010). Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples. Evid. -Based Complementary Altern. Med., 7.","DOI":"10.1093\/ecam\/nem177"},{"key":"ref_22","unstructured":"Rho, M.C., Kim, Y.K., Lee, H.S., Jun, C.D., Kim, K., Lee, S.W., Choi, J.H., and Song, G.Y. (2008). New acyclic triterpenoids compound, and pharmaceutical composition comprising Alpinia katsumadai extract or acyclic triterpenoids compounds isolated from the same. (Application No. WO\/2008\/133387), International Patent."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1136\/ard.51.11.1219","article-title":"Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases","volume":"51","author":"Farrell","year":"1992","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1172\/JCI115591","article-title":"In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis","volume":"89","author":"Sano","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1574-695X.2007.00329.x","article-title":"The role of nitric oxide in inflammatory reactions","volume":"51","author":"Tripathi","year":"2007","journal-title":"Fems Immunol. Med. Microbiol."},{"key":"ref_26","first-page":"30","article-title":"Selective inhibitors of cyclooxygenase-2","volume":"1","author":"Mardini","year":"2001","journal-title":"Mol. Interv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.4103\/0972-124X.55842","article-title":"Estimation of nitric oxide as an inflammatory marker in periodontitis","volume":"13","author":"Menaka","year":"2009","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_29","first-page":"771","article-title":"Cytokine storm in the pathogenesis of multiple organ dysfunction syndrome associated with surgical insults","volume":"97","author":"Aikawa","year":"1996","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1590\/S1806-37132008001100009","article-title":"Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis","volume":"34","author":"Peresi","year":"2008","journal-title":"J. Bras. Pneumol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1001\/archinte.167.15.1655","article-title":"Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study","volume":"167","author":"Kellum","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_32","first-page":"888","article-title":"Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264. 7 macrophages and DNCB-induced atopic dermatitis animal models","volume":"41","author":"Lee","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"532","DOI":"10.4062\/biomolther.2012.20.6.532","article-title":"Avicularin inhibits lipopolysaccharide-induced inflammatory response by suppressing ERK phosphorylation in RAW 264.7 macrophages","volume":"20","author":"Vo","year":"2012","journal-title":"Biomol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.4062\/biomolther.2016.026","article-title":"Quercetin-3-O-\u03b2-D-glucuronide suppresses lipopolysaccharide-induced JNK and ERK phosphorylation in LPS-challenged RAW264. 7 cells","volume":"24","author":"Park","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.brainres.2005.12.043","article-title":"Nonparticipation of nuclear factor kappa B (NF\u03baB) in the signaling cascade of c-Jun N-terminal kinase (JNK)-and p38 mitogen-activated protein kinase (p38MAPK)-dependent tumor necrosis factor alpha (TNF\u03b1) induction in lipopolysaccharide (LPS)-stimulated microglia","volume":"1073","author":"Uesugi","year":"2006","journal-title":"Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13777","DOI":"10.1073\/pnas.0605988103","article-title":"LPS-induced TNF-\u03b1 factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways","volume":"103","author":"Tang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6399","DOI":"10.3892\/mmr.2015.4243","article-title":"Lipopolysaccharide-induced tumor necrosis factor-\u03b1 factor enhances inflammation and is associated with cancer","volume":"12","author":"Zou","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_38","first-page":"1954","article-title":"l Lee, H.S.; Ku, S.K. Effect of exopolymers from Aureobasidium pullulans on formalin-induced chronic paw inflammation in mice","volume":"16","author":"Kim","year":"2006","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.5487\/TR.2011.27.2.095","article-title":"Effect of DHU001, a polyherbal formula on formalin-induced paw chronic inflammation of mice","volume":"27","author":"Cho","year":"2011","journal-title":"Toxicol. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/15\/3345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:51:09Z","timestamp":1760176269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/15\/3345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,23]]},"references-count":39,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["molecules25153345"],"URL":"https:\/\/doi.org\/10.3390\/molecules25153345","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,23]]}}}