{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:12:54Z","timestamp":1767852774703,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)\/prostaglandin (PG) E<jats:sub>2<\/jats:sub>production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE<jats:sub>2<\/jats:sub>in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1<jats:italic>\u03b2<\/jats:italic>in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-<jats:italic>\u03ba<\/jats:italic>B and AP-1 were targeted by AP736 via inhibition of the IKK\/I<jats:italic>\u03ba<\/jats:italic>B<jats:italic>\u03b1<\/jats:italic>and IRAK1\/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-<jats:italic>\u03ba<\/jats:italic>B-IKK\/I<jats:italic>\u03ba<\/jats:italic>B<jats:italic>\u03b1<\/jats:italic>and AP-1-IRAK1\/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.<\/jats:p>","DOI":"10.1155\/2014\/354843","type":"journal-article","created":{"date-parts":[[2014,10,19]],"date-time":"2014-10-19T17:02:54Z","timestamp":1413738174000},"page":"1-11","source":"Crossref","is-referenced-by-count":20,"title":["NF-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mi>\u03ba<\/mml:mi><\/mml:mrow><\/mml:math>B\/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton"],"prefix":"10.1155","volume":"2014","author":[{"given":"Van Thai","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heung Soo","family":"Beak","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang-Soo","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Jahangir","family":"Hossen","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"},{"name":"Department of Animal Science, Patuakhali Science and Technology University, Patuakhali 8602, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Seok","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-2474","authenticated-orcid":true,"given":"Jun Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-5135","authenticated-orcid":true,"given":"Sungjae","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0109-1739","authenticated-orcid":true,"given":"Jeong-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung Hyup","family":"Joo","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonho","family":"Choi","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Ju","family":"Shin","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungyoul","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song Seok","family":"Shin","sequence":"additional","affiliation":[{"name":"Medical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":true,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"3","key":"1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2174\/1871528113666140522112003","volume":"13","year":"2014","journal-title":"Inflammation & Allergy-Drug Targets"},{"issue":"3","key":"2","first-page":"214","volume":"12","year":"2014","journal-title":"Journal der Deutschen Dermatologischen Gesellschaft"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00890.x"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1159\/000087011"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.08R32FM"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2008.08.011"},{"issue":"6","key":"7","doi-asserted-by":"crossref","first-page":"644","DOI":"10.2340\/00015555-1197","volume":"91","year":"2011","journal-title":"Acta Dermato-Venereologica"},{"issue":"1","key":"8","first-page":"51","volume":"19","year":"2011","journal-title":"Acta Dermatovenerologica Croatica"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(00)00160-2"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2013.023"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.1.380"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.2001.00458.x"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2013.044"},{"issue":"3","key":"14","first-page":"s16","volume":"12","year":"2013","journal-title":"Journal of Drugs in Dermatology"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/S0151-9638(12)70130-8"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.12.144"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12248"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00337-X"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.5142\/jgr.2013.37.54"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.5142\/jgr.2013.37.300"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(00)00147-2"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.136"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.2.374"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.05.009"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(88)90134-6"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.5142\/jgr.2010.34.3.246"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-008-0232-x"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.08.011"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2013.001"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.0800.189"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.074872"},{"issue":"2","key":"32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.5142\/jgr.2011.35.2.200","volume":"35","year":"2011","journal-title":"Journal of Ginseng Research"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.5142\/jgr.2012.36.2.146"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.06.048"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23161"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.01.030"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00403-13"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.09.016"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/405158"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1112213"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2013.04.019"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/518183"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.10.006"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/787042"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1691\/ph.2011.0798"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8693-x"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056709"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.01.022"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12034"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/512926"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/979105"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.2741\/3702"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2014\/354843.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2014\/354843.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2014\/354843.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T18:41:09Z","timestamp":1498156869000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/mi\/2014\/354843\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":52,"alternative-id":["354843","354843"],"URL":"https:\/\/doi.org\/10.1155\/2014\/354843","relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}