{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:29:41Z","timestamp":1786649381053,"version":"build-2736575974"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Sepsis, a life-threatening systemic inflammatory condition, is a leading cause of mortality worldwide. Its pathophysiology involves the activation of nuclear factor kappa beta (NF-\u03baB), which promotes the release of proinflammatory cytokines. Acetylsalicylic acid (ASA), a widely used nonsteroidal anti-inflammatory drug, inhibits NF-\u03baB but poses risks of peptic ulcer disease and nephrotoxicity. This study evaluates the efficacy of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl), a novel salicylate derivative, in reducing NF-\u03baB expression in the kidneys and lungs of lipopolysaccharide (LPS)-induced septic BALB\/C mice. Mice were divided into four groups: untreated, LPS only, LPS + ASA (60 mg\/kg BW), and LPS + 3-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl (60 mg\/kg BW). NF-\u03baB expression was assessed via immunohistochemistry. LPS significantly increased NF-\u03baB expression in both renal and pulmonary tissues compared to controls (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001). While ASA treatment reduced NF-\u03baB levels (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001), 3-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl demonstrated superior suppression in the renal cortex, renal medulla, and alveolar regions (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05). In addition, 3-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl alleviated hypothermia in septic mice, comparable to ASA. Given its enhanced anti-inflammatory efficacy and reduced gastrointestinal risk, 3-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl presents a promising alternative to ASA for sepsis-related inflammation management. Further studies are warranted to explore its clinical applications.\n                  <\/jats:p>","DOI":"10.4103\/japtr.japtr_61_25","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T08:00:29Z","timestamp":1754726429000},"page":"163-168","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["2-((3-(chloromethyl) benzoyl) oxy) benzoic acid suppresses NF-\u03baB expression in the kidneys and lungs of LPS-Induced BALB\/C mice"],"prefix":"10.4103","volume":"16","author":[{"given":"Kuncoro","family":"Foe","sequence":"first","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipus","family":"Karel","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Ervina","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudy","family":"Tjahjono","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendy","family":"Wijaya","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette Dian Novita","family":"Dewi","sequence":"additional","affiliation":[{"name":"Departement of Pharmacology, Faculty of Medicine, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claritta Angelina Wiyanto","family":"Putri","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fransiskus Regis","family":"Partana","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Angelina","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sianty","family":"Dewi","sequence":"additional","affiliation":[{"name":"Departement of Pharmacology, Faculty of Medicine, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senny Yesery","family":"Esar","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuryanto","family":"Hadinugroho","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hevi","family":"Wihadmadyatami","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Veterinary Medicine, Gadjah Mada University, Karangmalang, Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Caroline","sequence":"additional","affiliation":[{"name":"Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"R1-20260421","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI11830","article-title":"NF-kappaB: A key role in inflammatory diseases","volume":"107","author":"Tak","year":"2001","journal-title":"J Clin Invest"},{"key":"R2-20260421","doi-asserted-by":"crossref","first-page":"L622","DOI":"10.1152\/ajplung.00477.2005","article-title":"NF-kappa B activation as a pathological mechanism of septic shock and inflammation","volume":"290","author":"Liu","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"R3-20260421","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1021\/ja5112964","article-title":"Mechanistic insights into a classic wonder drug \u2013 Aspirin","volume":"137","author":"Lei","year":"2015","journal-title":"J Am Chem Soc"},{"key":"R4-20260421","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1021\/acsomega.2c05566","article-title":"Synthesis, characterization, and application of 2-((3-(Chloromethyl)-benzoyl)oxy)benzoic acid: A review","volume":"8","author":"Tjahjono","year":"2023","journal-title":"ACS Omega"},{"key":"R5-20260421","doi-asserted-by":"crossref","first-page":"106364","DOI":"10.1016\/j.prostaglandins.2019.106364","article-title":"Evaluation of analgesic and antiplatelet activity of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid","volume":"145","author":"Caroline","year":"2019","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"R6-20260421","first-page":"15","volume":"13","author":"Tamayanti","year":"2016","journal-title":"Analgesic Activity Test of 2-(3-(Chloromethyl)benzoyloxy)benzoic Acid and 2-(4-(Chloromethyl)benzoyloxy)benzoic Acid in Male Wistar Rats Using the Plantar Test Method; Journal of Pharmaceutical Sciences and Community"},{"key":"R7-20260421","doi-asserted-by":"crossref","first-page":"106549","DOI":"10.1016\/j.prostaglandins.2021.106549","article-title":"Anti-inflammatory activity of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid in LPS-induced rat model","volume":"154","author":"Tjahjono","year":"2021","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"R8-20260421","doi-asserted-by":"crossref","first-page":"617314","DOI":"10.3389\/fphar.2021.617314","article-title":"Oleuropein attenuates lipopolysaccharide-induced acute kidney injury in vitro and in vivo by regulating toll-like receptor 4 dimerization","volume":"12","author":"Cui","year":"2021","journal-title":"Front Pharmacol"},{"key":"R9-20260421","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/bph.15966","article-title":"Fifty years with aspirin and platelets","volume":"180","author":"Patrono","year":"2023","journal-title":"Br J Pharmacol"},{"key":"R10-20260421","doi-asserted-by":"crossref","first-page":"279","DOI":"10.22159\/ijap.2019v11i5.34536","article-title":"Characterization of pharmacokinetics of 2-((3-(chloromethyl) benzoyl) oxy) benzoic acid in rats by using hplc-dad method","volume":"11","author":"Caroline","year":"2019","journal-title":"Int J Appl Pharm"},{"key":"R11-20260421","doi-asserted-by":"crossref","first-page":"34045","DOI":"10.1021\/acsomega.2c03147","article-title":"Tablet formulation of 2-((3-(Chloromethyl)benzoyl)oxy) benzoic acid by linear and quadratic models","volume":"7","author":"Hadinugroho","year":"2022","journal-title":"ACS Omega"},{"key":"R12-20260421","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0306-9877(98)90022-6","article-title":"Mini-symposium on clinical thermophyslology: New hypotheses and emerging concepts fever and hypothermia: Two adaptive thermoregulatory responses to systemic inflammation","volume":"50","author":"Romanovsky","year":"1998","journal-title":"Med Hypotheses"},{"key":"R13-20260421","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jneuroim.2007.06.020","article-title":"Neuronal NF-kappaB influences thermoregulation and survival in a sepsis model","volume":"189","author":"J\u00fcttler","year":"2007","journal-title":"J Neuroimmunol"},{"key":"R14-20260421","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.neuropharm.2007.10.017","article-title":"The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition","volume":"54","author":"Gong","year":"2008","journal-title":"Neuropharmacology"},{"key":"R15-20260421","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/23948","article-title":"The anti-inflammatory agents aspirin and salicylate inhibit the activity of I\u03baB kinase-\u03b2","volume":"396","author":"Gaynor","year":"1998","journal-title":"Nature"},{"key":"R16-20260421","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"R17-20260421","doi-asserted-by":"crossref","first-page":"7966","DOI":"10.1128\/MCB.25.18.7966-7975.2005","article-title":"NF-kappaB RelA phosphorylation regulates RelA acetylation","volume":"25","author":"Chen","year":"2005","journal-title":"Mol Cell Biol"},{"key":"R18-20260421","doi-asserted-by":"crossref","first-page":"106866","DOI":"10.1016\/j.prostaglandins.2024.106866","article-title":"2-(3-(Chloromethyl)benzoyloxy)benzoic Acid reduces prostaglandin E-2 concentration, NOX2 and NF\u03baB expression, ROS production, and COX-2 expression in lipopolysaccharide-induced mice","volume":"174","author":"Tjahjono","year":"2024","journal-title":"Prostaglandins and Other Lipid Mediators"}],"container-title":["Journal of Advanced Pharmaceutical Technology &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_61_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:53:23Z","timestamp":1786647203000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_61_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/japtr.japtr_61_25","relation":{},"ISSN":["2231-4040","0976-2094"],"issn-type":[{"value":"2231-4040","type":"print"},{"value":"0976-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-03-12","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}