{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:37:55Z","timestamp":1785285475817,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Development Research Foundation of NIFDC","award":["2020A1"],"award-info":[{"award-number":["2020A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Brucine (BRU) and brucine N-oxide (BNO) are prominent, bioactive, and toxic alkaloids in crude and processed Semen Strychni. Studies have demonstrated that BRU and BNO possess comprehensive pharmacological activities, such as anti-inflammatory and analgesic. In this context, a comparative study of BRU and BNO was performed by combination analysis of in silico ADMET prediction, in vivo toxicity evaluation, and potential action mechanism exploration. ADMET prediction showed that BRU and BNO might induce liver injury, and BRU may have a stronger hepatoxic effect. The prediction was experimentally verified using the zebrafish model. The BRU-induced hepatotoxicity of zebrafish larvae had a dose-response relationship. The mechanism of BRU-induced hepatotoxicity might relate to phosphorylation, kinase activity, and signal transduction. By comparison, signal transduction and gap junctions might involve BNO-induced hepatotoxicity. Our results provided a better understanding of BRU- and BNO-induced hepatotoxicity. We also built a foundation to elucidate the material base of the hepatotoxicity of traditional Chinese medicine Semen Strychni.<\/jats:p>","DOI":"10.3390\/molecules28031341","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T01:36:59Z","timestamp":1675215419000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Combination of In Silico ADMET Prediction, In Vivo Toxicity Evaluation, and Potential Mechanism Exploration of Brucine and Brucine N-oxide\u2014A Comparative Study"],"prefix":"10.3390","volume":"28","author":[{"given":"Yan","family":"Gao","sequence":"first","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingpu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Dai","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangcheng","family":"Ma","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/acer.14344","article-title":"Brucine N-Oxide Reduces Ethanol Intake and Preference in Alcohol-Preferring Male Fawn-Hooded Rats","volume":"44","author":"Wei","year":"2020","journal-title":"Alcohol Clin. 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