{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:29:34Z","timestamp":1785439774110,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["2017R1A5A2015541"],"award-info":[{"award-number":["2017R1A5A2015541"]}]},{"name":"National Research Foundation of Korea","award":["2019R1A2C1090178"],"award-info":[{"award-number":["2019R1A2C1090178"]}]},{"name":"National Research Foundation of Korea","award":["20182MFDS425"],"award-info":[{"award-number":["20182MFDS425"]}]},{"name":"National Research Foundation of Korea","award":["2022RIS-001"],"award-info":[{"award-number":["2022RIS-001"]}]},{"name":"Korean Food and Drug Administration","award":["2017R1A5A2015541"],"award-info":[{"award-number":["2017R1A5A2015541"]}]},{"name":"Korean Food and Drug Administration","award":["2019R1A2C1090178"],"award-info":[{"award-number":["2019R1A2C1090178"]}]},{"name":"Korean Food and Drug Administration","award":["20182MFDS425"],"award-info":[{"award-number":["20182MFDS425"]}]},{"name":"Korean Food and Drug Administration","award":["2022RIS-001"],"award-info":[{"award-number":["2022RIS-001"]}]},{"name":"Regional Innovation Strategy grant from the Ministry of Education, South Korea","award":["2017R1A5A2015541"],"award-info":[{"award-number":["2017R1A5A2015541"]}]},{"name":"Regional Innovation Strategy grant from the Ministry of Education, South Korea","award":["2019R1A2C1090178"],"award-info":[{"award-number":["2019R1A2C1090178"]}]},{"name":"Regional Innovation Strategy grant from the Ministry of Education, South Korea","award":["20182MFDS425"],"award-info":[{"award-number":["20182MFDS425"]}]},{"name":"Regional Innovation Strategy grant from the Ministry of Education, South Korea","award":["2022RIS-001"],"award-info":[{"award-number":["2022RIS-001"]}]},{"name":"academic research program of Chungbuk National University","award":["2017R1A5A2015541"],"award-info":[{"award-number":["2017R1A5A2015541"]}]},{"name":"academic research program of Chungbuk National University","award":["2019R1A2C1090178"],"award-info":[{"award-number":["2019R1A2C1090178"]}]},{"name":"academic research program of Chungbuk National University","award":["20182MFDS425"],"award-info":[{"award-number":["20182MFDS425"]}]},{"name":"academic research program of Chungbuk National University","award":["2022RIS-001"],"award-info":[{"award-number":["2022RIS-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Psoriasis, a chronic inflammation-mediated skin disease, affects 2\u20133% of the global population. It is characterized by keratinocyte hyperproliferation and immune cell infiltration. The JAK\/STAT3 and JAK\/STAT1 signaling pathways play an important role in the development of psoriasis when triggered by IL-6 and IFN-\u03b3, which are produced by dendritic cells and T-lymphocytes. Thus, blocking JAK\/STAT signaling may be a potential strategy for treating psoriasis. Therefore, we examined the effects of CMX, an extract of Centipeda minima enriched in Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C, on macrophages and keratinocytes. We established an in vitro model of psoriasis, based on an inflammation-associated keratinocyte proliferation model, and used macrophages and keratinocytes treated with LPS, IL-6, or IFN-\u03b3 to evaluate the effect of CMX. We found that CMX reduced pro-inflammatory cytokine production, by inhibiting lipopolysaccharide (LPS)-induced JAK1\/2 and STAT1\/3 phosphorylation in macrophages. Moreover, CMX-downregulated chemokine expression and cell proliferation compared with components in HaCaT cells, induced by rh-IL-6 and rh-IFN-\u03b3, respectively. Consistently, we demonstrated that the reduction in chemokine expression and hyperproliferation was mediated by the regulation of IFN-\u03b3-activated JAK\/STAT1 and IL-6-activated JAK\/STAT3 signaling. In conclusion, CMX inhibited JAK\/STAT-mediated inflammatory responses and cell proliferation in macrophages and keratinocytes. Consequently, CMX may have potential uses as a therapeutic agent for treating psoriasis.<\/jats:p>","DOI":"10.3390\/molecules28041723","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T02:14:11Z","timestamp":1676254451000},"page":"1723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Centipeda minima Extract Inhibits Inflammation and Cell Proliferation by Regulating JAK\/STAT Signaling in Macrophages and Keratinocytes"],"prefix":"10.3390","volume":"28","author":[{"given":"Yuanqiang","family":"Ma","sequence":"first","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Ha","family":"Kim","sequence":"additional","affiliation":[{"name":"D. Nature Co., Ltd., Seongnam 13174, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Kyu","family":"Yun","sequence":"additional","affiliation":[{"name":"D. Nature Co., Ltd., Seongnam 13174, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Seok","family":"Roh","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/bjd.15021","article-title":"Incidence, prevalence and mortality of patients with psoriasis: A U.K. population-based cohort study","volume":"176","author":"Springate","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e006450","DOI":"10.1136\/bmjopen-2014-006450","article-title":"Epidemiology of psoriasis and palmoplantar pustulosis: A nationwide study using the Japanese national claims database","volume":"5","author":"Kubota","year":"2015","journal-title":"Bmj Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e028116","DOI":"10.1136\/bmjopen-2018-028116","article-title":"Prevalence and characteristics of psoriasis in Denmark: Findings from the Danish skin cohort","volume":"9","author":"Egeberg","year":"2019","journal-title":"Bmj Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ejphar.2017.07.040","article-title":"Imiquimod-induced psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin","volume":"813","author":"Varma","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109615","DOI":"10.1016\/j.biopha.2019.109615","article-title":"Convallatoxin induces HaCaT cell necroptosis and ameliorates skin lesions in psoriasis-like mouse models","volume":"121","author":"Jiang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sun, J., Zhao, Y., and Hu, J.H. (2013). Curcumin Inhibits Imiquimod-Induced Psoriasis-Like Inflammation by Inhibiting IL-1beta and IL-6 Production in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067078"},{"key":"ref_7","first-page":"139","article-title":"Psoriasis: Pathogenesis and treatment","volume":"24","author":"Heenen","year":"2003","journal-title":"Rev. Med. Brux."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/jid.2013.500","article-title":"Periostin controls keratinocyte proliferation and differentiation by interacting with the paracrine IL-1alpha\/IL-6 loop","volume":"134","author":"Taniguchi","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"738481","DOI":"10.3389\/fimmu.2021.738481","article-title":"Tofacitinib Suppresses Several JAK-STAT Pathways in Rheumatoid Arthritis In Vivo and Baseline Signaling Profile Associates with Treatment Response","volume":"12","author":"Palmroth","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41575-020-0273-0","article-title":"JAK-STAT pathway targeting for the treatment of inflammatory bowel disease","volume":"17","author":"Salas","year":"2020","journal-title":"Nat. Rev. Gastro. Hepat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000452526","article-title":"Inhibition of STAT Pathway Impairs Anti Hepatitis C Virus Effect of Interferon Alpha","volume":"40","author":"Zhao","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_12","first-page":"185","article-title":"A Scoping Review on Use of Drugs Targeting the JAK\/STAT Pathway in Psoriasis","volume":"9","author":"Ruano","year":"2022","journal-title":"Front. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/bjd.12049","article-title":"STAT1 expression and activation is increased in lesional psoriatic skin","volume":"168","author":"Hald","year":"2013","journal-title":"Brit. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Calautti, E., Avalle, L., and Poli, V. (2018). Psoriasis: A STAT3-Centric View. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010171"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jsps.2017.04.034","article-title":"Acitretin modulates HaCaT cells proliferation through STAT1-and STAT3-dependent signaling","volume":"25","author":"Qin","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, X., Du, Y.P., Nan, J., Zhang, X.X., Qin, X.D., Wang, Y.X., Hou, J.W., Wang, Q., and Yang, J.B. (2013). Brevilin A, a Novel Natural Product, Inhibits Janus Kinase Activity and Blocks STAT3 Signaling in Cancer Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063697"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liu, R., Chan, B.D., Mok, D.K.W., Lee, C.S., Tai, W.C.S., and Chen, S.B. (2019). Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma. Molecules, 24.","DOI":"10.3390\/molecules24101908"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kim, B.H., Lee, M.J., Lee, W.Y., Pyo, J., Shin, M.S., Hwang, G.S., Shin, D., Kim, C.E., Park, E.S., and Kang, K.S. (2021). Hair Growth Stimulation Effect of Centipeda minima Extract: Identification of Active Compounds and Anagen-Activating Signaling Pathways. Biomolecules, 11.","DOI":"10.3390\/biom11070976"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112229","DOI":"10.1016\/j.biopha.2021.112229","article-title":"Anti-psoriatic and anti-inflammatory effects of Kaempferia parviflora in keratinocytes and macrophage cells","volume":"143","author":"Takuathung","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5087847","DOI":"10.1155\/2019\/5087847","article-title":"Interleukin 6 Function in the Skin and Isolated Keratinocytes Is Modulated by Hyperglycemia","volume":"2019","author":"Lee","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jid.2016.09.016","article-title":"Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease","volume":"137","author":"Richmond","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7897263","DOI":"10.1155\/2018\/7897263","article-title":"Selective Immunomodulation of Inflammatory Pathways in Keratinocytes by the Janus Kinase (JAK) Inhibitor Tofacitinib: Implications for the Employment of JAK-Targeting Drugs in Psoriasis","volume":"2018","author":"Morelli","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tokuyama, M., and Mabuchi, T. (2020). New Treatment Addressing the Pathogenesis of Psoriasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207488"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaad.2016.12.005","article-title":"JAK inhibitors in dermatology: The promise of a new drug class","volume":"76","author":"Damsky","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41419-019-1510-8","article-title":"Berberine downregulates CDC6 and inhibits proliferation via targeting JAK-STAT3 signaling in keratinocytes","volume":"10","author":"Sun","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Choi, M., Yi, J.K., Kim, S.Y., Ryu, J.H., Lee, J., Kwon, W., Jang, S., Kim, D., Kim, M., and Kim, H. (2019). Anti-inflammatory effects of a methanol extract of Dictamnus dasycarpus Turcz. root bark on imiquimod-induced psoriasis. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2767-2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s12276-021-00620-z","article-title":"2\u2019-Hydroxycinnamaldehyde ameliorates imiquimod-induced psoriasiform inflammation by targeting PKM2-STAT3 signaling in mice","volume":"53","author":"Hao","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11926-007-0075-1","article-title":"Pathophysiology of psoriasis: Recent advances on IL-23 and Th17 cytokines","volume":"9","author":"Fitch","year":"2007","journal-title":"Curr. Rheumatol. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1723\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:31:13Z","timestamp":1760121073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,11]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041723"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041723","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,11]]}}}