PMID- 30064139 OWN - NLM STAT- MEDLINE DCOM- 20180914 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 48 IP - 4 DP - 2018 TI - Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation. PG - 1468-1479 LID - 10.1159/000492257 [doi] AB - BACKGROUND/AIMS: Zedoarondiol, a sesquiterpene lactone compound, showed an anti-proliferative activity on vascular smooth muscle cells in our previous study. However, whether it has a beneficial effect on endothelial cells injury induced by oxidized low-density lipoprotein (ox-LDL) remains unclear. This study was designed to investigate the protective effect of zedoarondiol on ox-LDL-induced injury of endothelial cells and explored its underlying mechanism. METHODS: The protective effect of zedoarondiol on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury were evaluated by Cell Counting Kit-8 (CCK-8) assay and released lactic dehydrogenase (LDH) activity assay. Oxidative stress was determined by malonedialdehyde (MDA) content and superoxide dismutase (SOD) activity. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The culture supernatant was collected for enzyme linked immune-sorbent assays (ELISA) of interleukine-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence staining was used to observe NF-E2-related factor 2 (Nrf2) translocation. Western blotting was performed to determine the expression of IL-1beta, TNF-alpha, MCP-1, Kelch-like ECH associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and Nrf2. RESULTS: Zedoarondiol attenuated HUVECs injury, up-regulated SOD activity, suppressed formation of MDA and ROS, and secretion and protein expression of IL-1beta, TNF-alpha, and MCP-1 in injured HUVECs induced by ox-LDL. Zedoarondiol induced nuclear Nrf2 translocation from cytoplasm into nucleus and up-regulated expression of HO-1, NQO1, and Nrf2 in nucleus. All-trans-retinoic acid (ATRA), an inhibitor of Nrf2, abolished zedoarondiol-mediated anti-oxidative effect. CONCLUSION: Zedoarondiol attenuates ox-LDL-induced endothelial cells injury by inhibiting oxidative stress and inflammation via Nrf2/HO-1 pathway, suggesting that zedoarondiol might be meaningful on prevention and treatment of atherosclerosis. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Mao, Huimin AU - Mao H AD - Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. AD - Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Tao, Tianqi AU - Tao T AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Xiaoren AU - Wang X AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Liu, Mi AU - Liu M AD - Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Song, Dandan AU - Song D AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Liu, Xiuhua AU - Liu X AD - Department of Pathophysiology, Chinese PLA General Hospital, Beijing, China. FAU - Shi, Dazhuo AU - Shi D AD - Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. LA - eng PT - Journal Article DEP - 20180731 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (KEAP1 protein, human) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (Lactones) RN - 0 (Lipoproteins, LDL) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Reactive Oxygen Species) RN - 0 (Sesquiterpenes) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (oxidized low density lipoprotein) RN - 0 (zedoarondiol) RN - 4Y8F71G49Q (Malondialdehyde) RN - 5688UTC01R (Tretinoin) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, human) SB - IM MH - Cell Survival/drug effects MH - Chemokine CCL2/analysis MH - Heme Oxygenase-1/metabolism MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Interleukin-1beta/analysis MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - L-Lactate Dehydrogenase/metabolism MH - Lactones/*pharmacology MH - Lipoproteins, LDL/*toxicity MH - Malondialdehyde/metabolism MH - NAD(P)H Dehydrogenase (Quinone)/metabolism MH - NF-E2-Related Factor 2/antagonists & inhibitors/*metabolism MH - Oxidative Stress/*drug effects MH - Reactive Oxygen Species/metabolism MH - Sesquiterpenes/*pharmacology MH - Superoxide Dismutase/metabolism MH - Tretinoin/pharmacology MH - Tumor Necrosis Factor-alpha/analysis OTO - NOTNLM OT - Endothelial cells OT - Inflammation OT - Nrf2 OT - Oxidative stress OT - Zedoarondiol EDAT- 2018/08/01 06:00 MHDA- 2018/09/15 06:00 CRDT- 2018/08/01 06:00 PHST- 2017/04/15 00:00 [received] PHST- 2018/07/20 00:00 [accepted] PHST- 2018/08/01 06:00 [pubmed] PHST- 2018/09/15 06:00 [medline] PHST- 2018/08/01 06:00 [entrez] AID - 000492257 [pii] AID - 10.1159/000492257 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;48(4):1468-1479. doi: 10.1159/000492257. Epub 2018 Jul 31.