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Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
Department of Anesthesiology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510080, China
Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism, Sun Yat-Sen University, Bureau of Education, Guangzhou 510080, China
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 28 November 2012; in revised form: 22 January 2013 / Accepted: 31 January 2013 / Published: 18 February 2013
Abstract: 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.
Keywords: xyloketal B; apoptosis; reactive oxygen species; HO-1; Nrf-2
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Li, Z.-X.; Chen, J.-W.; Yuan, F.; Huang, Y.-Y.; Zhao, L.-Y.; Li, J.; Su, H.-X.; Liu, J.; Pang, J.-Y.; Lin, Y.-C.; Lu, X.-L.; Pei, Z.; Wang, G.-L.; Guan, Y.-Y. Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish. Mar. Drugs 2013, 11, 504-522.
Li Z-X, Chen J-W, Yuan F, Huang Y-Y, Zhao L-Y, Li J, Su H-X, Liu J, Pang J-Y, Lin Y-C, Lu X-L, Pei Z, Wang G-L, Guan Y-Y. Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish. Marine Drugs. 2013; 11(2):504-522.
Li, Zhen-Xing; Chen, Jian-Wen; Yuan, Feng; Huang, Yun-Ying; Zhao, Li-Yan; Li, Jie; Su, Huan-Xing; Liu, Jie; Pang, Ji-Yan; Lin, Yong-Cheng; Lu, Xi-Lin; Pei, Zhong; Wang, Guan-Lei; Guan, Yong-Yuan. 2013. "Xyloketal B Exhibits Its Antioxidant Activity through Induction of HO-1 in Vascular Endothelial Cells and Zebrafish." Mar. Drugs 11, no. 2: 504-522.