{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:53:19Z","timestamp":1787979199999,"version":"build-2784847793"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jeju National University","award":["B0234"],"award-info":[{"award-number":["B0234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Drug repurposing is a simple concept with a long history, and is a paradigm shift that can significantly reduce the costs and accelerate the process of bringing a new small-molecule drug into clinical practice. We attempted to uncover a new application of spiramycin, an old medication that was classically prescribed for toxoplasmosis and various other soft-tissue infections; specifically, we initiated a study on the anti-inflammatory capacity of spiramycin. For this purpose, we used murine macrophage RAW 264.7 as a model for this experiment and investigated the anti-inflammatory effects of spiramycin by inhibiting the production of pro-inflammatory mediators and cytokines. In the present study, we demonstrated that spiramycin significantly decreased nitric oxide (NO), interleukin (IL)-1\u03b2, and IL-6 levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Spiramycin also inhibited the expression of NO synthase (iNOS), potentially explaining the spiramycin-induced decrease in NO production. In addition, spiramycin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) as well as the inactivation and subsequent nuclear translocation of nuclear factor \u03baB (NF-\u03baB). This indicated that spiramycin attenuates macrophages\u2019 secretion of IL-6, IL-1\u03b2, and NO, inducing iNOS expression via the inhibition of the NF-\u03baB and MAPK signaling pathways. Finally, we tested the potential application of spiramycin as a topical material by human skin primary irritation tests. It was performed on the normal skin (upper back) of 31 volunteers to determine whether 100 \u03bcM and \u03bcM of spiramycin had irritation or sensitization potential. In these assays, spiramycin did not induce any adverse reactions. In conclusion, our results demonstrate that spiramycin can effectively attenuate the activation of macrophages, suggesting that spiramycin could be a potential candidate for drug repositioning as a topical anti-inflammatory agent.<\/jats:p>","DOI":"10.3390\/molecules27103202","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"3202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages"],"prefix":"10.3390","volume":"27","author":[{"given":"Jin-Kyu","family":"Kang","sequence":"first","affiliation":[{"name":"Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Kyu","family":"Kang","sequence":"additional","affiliation":[{"name":"Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3000-7989","authenticated-orcid":false,"given":"Chang-Gu","family":"Hyun","sequence":"additional","affiliation":[{"name":"Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jphp.13273","article-title":"Drug repositioning: A brief overview","volume":"72","author":"Jourdan","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1080\/17460441.2021.1912733","article-title":"Is drug repurposing really the future of drug discovery or is new innovation truly the way forward?","volume":"16","author":"Gil","year":"2021","journal-title":"Expert Opin. Drug. Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cbpa.2021.06.001","article-title":"Recent advances in drug repurposing using machine learning","volume":"65","author":"Urbina","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"752174","DOI":"10.3389\/fphar.2021.752174","article-title":"Drug-Repositioning Approaches Based on Medical and Life Science Databases","volume":"12","author":"Zamami","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.12793\/tcp.2021.29.e18","article-title":"The use of real-world data in drug repurposing","volume":"29","author":"Park","year":"2021","journal-title":"Transl. Clin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s40001-021-00606-7","article-title":"A fresh look at the role of spiramycin in preventing a neglected disease: Meta-analyses of observational studies","volume":"11","author":"Montoya","year":"2021","journal-title":"Eur. J. Med. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Elazab, S.T., Elshater, N.S., Hashem, Y.H., Al-Atfeehy, N.M., Lee, E.B., Park, S.C., and Hsu, W.H. (2021). Pharmacokinetic\/Pharmacodynamic Modeling of Spiramycin against Mycoplasma synoviae in Chickens. Pathogens, 10.","DOI":"10.3390\/pathogens10101238"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1007\/s12639-021-01396-9","article-title":"Effect of spiramycin versus aminoguanidine and their combined use in experimental toxoplasmosis","volume":"45","author":"Omar","year":"2021","journal-title":"J. Parasit. Dis."},{"key":"ref_9","first-page":"115","article-title":"The effect of spiramycin on Porphyromonas gingivalis and other \u201cclassic\u201d periopathogens","volume":"24","author":"Chiappe","year":"2011","journal-title":"Acta. Odontol. Latinoam."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.anaerobe.2011.03.017","article-title":"Spiramycin resistance in human periodontitis microbiota","volume":"17","author":"Rams","year":"2011","journal-title":"Anaerobe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ijantimicag.2018.12.009","article-title":"Spiramycin and azithromycin, safe for administration to children, exert antiviral activity against enterovirus A71 in vitro and in vivo","volume":"53","author":"Zeng","year":"2019","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kim, M.O., Ryu, H.W., Choi, J.H., Son, T.H., Oh, S.R., Lee, H.S., Yuk, H.J., Cho, S., Kang, J.S., and Lee, C.W. (2016). Anti-Obesity Effects of Spiramycin In Vitro and In Vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158632"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.carbpol.2018.11.039","article-title":"In vitro immunomodulatory effects of human milk oligosaccharides on murine macrophage RAW264.7 cells","volume":"207","author":"Zhang","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jgar.2021.09.003","article-title":"In vitro activity of non-antibiotic drugs against Staphylococcus aureus clinical strains","volume":"27","author":"Boyd","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jep.2017.08.034","article-title":"Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-\u03baB and Erk1\/2 signaling pathways in LPS-induced Raw264.7 cells","volume":"210","author":"Zou","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.gene.2018.06.057","article-title":"Anti-inflammatory effect of Calycosin glycoside on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells","volume":"675","author":"Dong","year":"2018","journal-title":"Gene"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kang, J.K., Chung, Y.C., and Hyun, C.G. (2021). Anti-Inflammatory Effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and NF-\u03baB Signaling Pathways. Molecules, 26.","DOI":"10.3390\/molecules26175351"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kang, J.K., and Hyun, C.G. (2020). 4-Hydroxy-7-Methoxycoumarin Inhibits Inflammation in LPS-activated RAW264.7 Macrophages by Suppressing NF-\u03baB and MAPK Activation. Molecules, 25.","DOI":"10.3390\/molecules25194424"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110557","DOI":"10.1016\/j.mehy.2021.110557","article-title":"Etoricoxib may inhibit cytokine storm to treat COVID-19","volume":"150","author":"Wang","year":"2021","journal-title":"Med. Hypotheses"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/exd.14299","article-title":"Redirecting drug repositioning to discover innovative cosmeceuticals","volume":"30","author":"Sotiropoulou","year":"2021","journal-title":"Exp. 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