Original Research ARTICLE
TTB Protects Astrocytes Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Activation of Nrf2/HO-1 Signaling Pathway
- 1Medical College, Yangzhou University, China
- 2Medical College, Yangzhou University, China
Neonatal hypoxia/ischemic encephalopathy (NHIE) is a severe condition that occurs death or neurological disability in newborns. The underlying pathological mechanisms are unclear and developing the target neuroprotective strategies are urgent. 2,7,2'-trihydroxy-4,4',7'-trimethoxy-1,1'-biphenanthrene (TTB) is a natural product isolated from Cremastra appendiculata (D. Don) Makino and Liparis nervosa (Thunb.) Lindl. TTB has demonstrated potent cytotoxic activity against stomach (HGC-27) and colon (HT-29) cancer cell lines. However, none of studies have addressed the effects of TTB in NHIE. In the present study, an oxygen-glucose deprivation/ reoxygenation (OGD/R)-induced astrocytes injury model was established to investigate the effect of TTB and its potential mechanisms. Our results showed that TTB alleviated the OGD/R-induced reactive oxygen species (ROS) increase and the intracellular antioxidant capacity of superoxide dismutase (SOD) activity decrease. Moreover, TTB potentially prolonged activation state of nuclear factor erythroid-2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and maintained the protection against oxidative stress in OGD/R-induced astrocytes by inducing the nuclear translocation and the upregulation of Nrf2, along with enhanced expression of downstream target gene HO-1. Furthermore, TTB treatment diminished the accumulation of hypoxia induced factor 1α (HIF1α) and vascular endothelial growth factor (VEGF) expression induced by OGD/R. We also found TTB-treated astrocytes reversed the inhibition of OGD/R on neurites growth of neurons by astrocyte-neuron co-culture system. In conclusion, TTB inhibited OGD/R-induced astrocytes oxidative stress, at least partially through inhibition of HIF1α and VEGF via Nrf2/HO-1 signaling pathway.
Keywords: neonatal hypoxia/ischemic encephalopathy, TTB, Oxygen-glucose deprivation/reoxygenation, Astrocytes, Nrf2/HO-1 signaling pathway, HIF1α, VEGF
Received: 28 Mar 2019;
Accepted: 18 Jun 2019.
Edited by:Stefania Ceruti, University of Milan, Italy
Reviewed by:Zhouguang Wang, Albert Einstein College of Medicine, United States
Marta Boccazzi, University of Milan, Italy
Copyright: © 2019 Liu, Zhao, Yin and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Liang Liu, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu Province, China, email@example.com
Mx. Xiaolu Zhang, Medical College, Yangzhou University, Yangzhou, China, firstname.lastname@example.org