{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:27:43Z","timestamp":1788276463940,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000262733"],"award-info":[{"award-number":["RS\u20102023\u201000262733"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201024535474"],"award-info":[{"award-number":["RS\u20102025\u201024535474"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The use of\n                    <jats:italic>Indigo naturalis<\/jats:italic>\n                    in treating inflammatory diseases is clinically restricted by severe adverse events, including pulmonary arterial hypertension and hepatotoxicity. Tryptanthrin, a major indoloquinazoline alkaloid of\n                    <jats:italic>Indigo naturalis<\/jats:italic>\n                    , exhibits potent anti\u2010inflammatory activity; however, its specific safety profile relative to the crude extract remains unclear. This study aimed to elucidate the intravenous pharmacokinetics and acute safety of purified tryptanthrin to validate its potential as a safer pharmacological alternative. Following a single intravenous injection of 30\u2009mg\/kg\u2014a dose range relevant to its pharmacological efficacy\u2014in ICR mice, plasma concentrations were quantified using a validated LC\u2013MS\/MS method. Tryptanthrin exhibited rapid systemic distribution and biphasic elimination, characterized by a large volume of distribution (V\n                    <jats:sub>ss<\/jats:sub>\n                    23.1\u2009L\/kg) and rapid clearance (6.54\u2009L\/h\/kg), indicating extensive tissue penetration and efficient systemic elimination. Importantly, over a 14\u2010day observation period, no mortality, behavioral abnormalities, or significant alterations in hepatic (AST, ALT, total bilirubin) and renal (BUN, creatinine) biochemical parameters were observed. These findings indicate that purified tryptanthrin does not induce the acute hepatic or renal toxicity frequently associated with crude\n                    <jats:italic>Indigo naturalis<\/jats:italic>\n                    preparations. This study provides the first pharmacokinetic characterization and safety validation of tryptanthrin at a therapeutic dose, supporting its preclinical development as a safe, single\u2010chemical entity for systemic administration.\n                  <\/jats:p>","DOI":"10.1002\/jat.70169","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T01:05:06Z","timestamp":1775696706000},"page":"3498-3505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Acute Safety Evaluation of Tryptanthrin, A Bioactive Constituent of Indigo naturalis, Following Intravenous Administration in Mice"],"prefix":"10.1002","volume":"46","author":[{"given":"Hyung\u00a0Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Natural Products &amp; Biotechnology Jeonbuk Science College  Jeongeup Jeollabuk\u2010do Republic of 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