{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:16:00Z","timestamp":1788617760691,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2013,2,18]],"date-time":"2013-02-18T00:00:00Z","timestamp":1361145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>We previously reported that a novel marine compound, xyloketal B, has strong antioxidative actions in different models of cardiovascular diseases. Induction of heme oxygenase-1 (HO-1), an important endogenous antioxidant enzyme, has been considered as a potential therapeutic strategy for cardiovascular diseases. We here investigated whether xyloketal B exhibits its antioxidant activity through induction of HO-1. In human umbilical vein endothelial cells (HUVECs), xyloketal B significantly induced HO-1 gene expression and translocation of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) in a concentration- and time-dependent manner. The protection of xyloketal B against angiotensin II-induced apoptosis and reactive oxygen species (ROS) production could be abrogated by the HO-1 specific inhibitor, tin protoporphyrin-IX (SnPP). Consistently, the suppressive effects of xyloketal B on NADPH oxidase activity could be reversed by SnPP in zebrafish embryos. In addition, xyloketal B induced Akt and Erk1\/2 phosphorylation in a concentration- and time-dependent manner. Furthermore, PI3K inhibitor LY294002 and Erk1\/2 inhibitor U0126 suppressed the induction of HO-1 and translocation of Nrf-2 by xyloketal B, whereas P38 inhibitor SB203580 did not. In conclusion, xyloketal B can induce HO-1 expression via PI3K\/Akt\/Nrf-2 pathways, and the induction of HO-1 is mainly responsible for the antioxidant and antiapoptotic actions of xyloketal B.<\/jats:p>","DOI":"10.3390\/md11020504","type":"journal-article","created":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T11:11:16Z","timestamp":1361272276000},"page":"504-522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish"],"prefix":"10.3390","volume":"11","author":[{"given":"Zhen-Xing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Xing","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yan","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510080, China"},{"name":"Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism,  Sun Yat-Sen University, Bureau of Education, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Cheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510080, China"},{"name":"Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism,  Sun Yat-Sen University, Bureau of Education, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Pei","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism,  Sun Yat-Sen University, Bureau of Education, Guangzhou 510080, China"},{"name":"Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"},{"name":"Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism,  Sun Yat-Sen University, Bureau of Education, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Yuan","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.bbalip.2006.02.017","article-title":"Protective effect of ebselen on cytotoxicity induced by cholestane-3 beta, 5 alpha, 6 beta-triol in ECV-304 cells","volume":"1761","author":"Wu","year":"2006","journal-title":"Biochim. 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