{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T23:55:05Z","timestamp":1785196505133,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research and Academic Services, Khon Kaen University","award":["RP63002"],"award-info":[{"award-number":["RP63002"]}]},{"name":"The Graduate School, Khon Kaen University for the Research Fund for Supporting Lecturer to Admit High Potential Student to Study and Research on His Expert Program","award":["581H219"],"award-info":[{"award-number":["581H219"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pineal gland is a neuroendocrine organ that plays an important role in anti-inflammation through the hormone melatonin. The anti-inflammatory effects of melatonin and its derivatives have been reported in both in vitro and in vivo models. Our previous study reported the potent antioxidant and neuroprotective activities of bromobenzoylamide substituted melatonin. In silico analysis successfully predicted that melatonin bromobenzoylamid derivatives were protected from metabolism by CYP2A1, which is a key enzyme of the melatonin metabolism process. Therefore, the anti-inflammatory activities of melatonin and its bromobenzoylamide derivatives BBM and EBM were investigated in LPS-induced RAW 264.7 macrophages and croton oil-induced ear edema in mice. The experiments showed that BBM and EBM significantly reduced production of the inflammatory mediators interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) in a dose-dependent manner, but only slightly affected TNF-\u03b1 in LPS-induced RAW 264.7 macrophages. This suggests that modifying melatonin at either the N1-position or the N-acetyl side chain affected production of NO, PGE2 and IL-6 in in vitro model. In the croton oil-induced mouse ear edema model, BBM, significantly decreased ear edema thickness at 2\u20134 h. It leads to conclude that bromobenzoylamide derivatives of melatonin may be one of the potential candidates for a new type of anti-inflammatory agent.<\/jats:p>","DOI":"10.3390\/molecules26144285","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T09:32:07Z","timestamp":1626341527000},"page":"4285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Anti-Inflammatory Comparison of Melatonin and Its Bromobenzoylamide Derivatives in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells and Croton Oil-Induced Mice Ear Edema"],"prefix":"10.3390","volume":"26","author":[{"given":"Pimpichaya","family":"Sangchart","sequence":"first","affiliation":[{"name":"Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-7132","authenticated-orcid":false,"given":"Panyada","family":"Panyatip","sequence":"additional","affiliation":[{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teerasak","family":"Damrongrungruang","sequence":"additional","affiliation":[{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Oral Diagnosis, Department of Oral Biomedical Sciences, Faculty of Dentistry, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aroonsri","family":"Priprem","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Mahasarakham University, Maha Sarakham 44150, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramote","family":"Mahakunakorn","sequence":"additional","affiliation":[{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-2071","authenticated-orcid":false,"given":"Ploenthip","family":"Puthongking","sequence":"additional","affiliation":[{"name":"Melatonin Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,15]]},"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":"2017","journal-title":"Oncotarget"},{"key":"ref_2","first-page":"882","article-title":"PI3K signalling in inflammation","volume":"1851","author":"Hawkins","year":"2015","journal-title":"Biochim. 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