AUTHOR=Lin Jialiang , Shi Yifeng , Miao Jiansen , Wu Yuhao , Lin Hao , Wu Jianwei , Zeng Weimin , Qi Fangzhou , Liu Chen , Wang Xiangyang , Jin Haiming 

TITLE=Gastrodin Alleviates Oxidative Stress-Induced Apoptosis and Cellular Dysfunction in Human Umbilical Vein Endothelial Cells via the Nuclear Factor-Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway and Accelerates Wound Healing In Vivo

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01273

DOI=10.3389/fphar.2019.01273

ISSN=1663-9812

ABSTRACT=<p><bold>Aims:</bold> To explore the effect and mechanism of gastrodin (GAS) on human umbilical vein endothelial cells (HUVECs) apoptosis induced by oxidative stress and its function in wound healing.</p><p><bold>Main methods:</bold> HUVECs were incubated with tert-butyl hydroperoxide (TBHP) to induce endothelial cell dysfunction and GAS was used as a protector. Cell viability was detected by Counting Kit-8 (CCK-8). HUVECs apoptosis was evaluated by TUNEL assay and western blotting for cleaved caspase3 (C-caspase3) and other apoptosis-related proteins. Transwell migration assay, tube formation assay, and cell-matrix adhesion assay were performed to evaluated cell function of HUVECs. Transfection with nuclear factor-erythroid 2-related factor 2 (<italic>Nrf2</italic>) small interfering ribonucleic acid and western blotting for <italic>Nrf2</italic>, HO-1, and apoptosis-related proteins were performed to prove that <italic>Nrf2</italic>/HO-1 pathway is involved in the protective effects of GAS. The skin wound model of rat was used to assess the protective effects of GAS <italic>in vivo</italic>.</p><p><bold>Key Findings:</bold> The results show that treating HUVECs with GAS attenuated TBHP-induced apoptosis and cellular dysfunction, including cellular tube formation, migration, and adhesion. Mechanistically, we found that GAS protects HUVECs from TBHP-induced cellular apoptosis by activating the nuclear factor (erythroid-derived 2)-like 2 (<italic>Nrf2</italic>)/heme oxygenase 1 (HO-1) pathway. An <italic>in vivo</italic> study illustrated that the oral administration of GAS enhances vascularization in regenerated tissue and facilitates wound healing.</p><p><bold>Significance:</bold> The findings of this study demonstrated that GAS may serve as a potential agent that accelerates wound healing.</p>