Int J Biol Sci 2019; 15(9):2016-2028. doi:10.7150/ijbs.30536

Research Paper

Artemisinin Protects Human Retinal Pigmented Epithelial Cells Against Hydrogen Peroxide-induced Oxidative Damage by Enhancing the Activation of AMP-active Protein Kinase

Shuai Li1,2#, Shubhash Chandra chaudhary1,2#, Xia Zhao1,2#, Uma Gaur1,2, Jiankang Fang1,2, Fengxia Yan1, Wenhua Zheng1,2✉

1. Center of Reproduction, Development & Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
2. Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
# These authors contributed equally to this work

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Citation:
Li S, chaudhary SC, Zhao X, Gaur U, Fang J, Yan F, Zheng W. Artemisinin Protects Human Retinal Pigmented Epithelial Cells Against Hydrogen Peroxide-induced Oxidative Damage by Enhancing the Activation of AMP-active Protein Kinase. Int J Biol Sci 2019; 15(9):2016-2028. doi:10.7150/ijbs.30536. Available from http://www.ijbs.com/v15p2016.htm

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Abstract

Dry age-related macular degeneration (AMD), a leading cause of blindness in aged population, is directly associated with oxidative stress induced damage of the retinal pigmented epithelial (RPE) cells. In the current study, we investigated the role of AMPK in the protective effect of artemisinin, an FDA approved anti-malarial Chinese herbal drug, on RPE cell line D407, against H2O2 induced oxidative stress. Our results showed that artemisinin promoted the survival of D407 cells from H2O2. Artemisinin reduced intracellular ROS generation and oxidative stress, decreased LDH release and the loss of mitochondrial membrane potential in D407 cells treated with H2O2. Western blotting showed that artemisinin concentration- and time-dependently stimulated the phosphorylation of AMP-activated protein kinase (AMPK) in D407 cells while AMPK inhibitor Compound C or knock-down of AMPK by si-RNA, inhibited the survival protective effect of artemisinin. More importantly, artemisinin produced a similar protective effect in primary cultured retinal pigment cells which was also blocked by inhibitors of AMPK. Taken together, these results suggested that artemisinin promotes survival of human retinal pigment cells against H2O2-induced cell death at least in part through enhancing the activation of AMPK. Therefore, artemisinin may be a beneficial therapeutic candidate for the treatment of age-related diseases, including retinal disorders like AMD.

Keywords: artemisinin, retinal pigment epithelial cells, oxidative stress, AMPK