Protective Effect of Flavonoids from a Deep-Sea-Derived <i>Arthrinium</i> sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells

Jia-Rong Hou; Yan-Hong Wang; Ying-Nan Zhong; Tong-Tong Che; Yang Hu; Jie Bao; Ning Meng

doi:10.3390/md19120712

Marine Drugs (Dec 2021)

Protective Effect of Flavonoids from a Deep-Sea-Derived <i>Arthrinium</i> sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells

Jia-Rong Hou,
Yan-Hong Wang,
Ying-Nan Zhong,
Tong-Tong Che,
Yang Hu,
Jie Bao,
Ning Meng

Affiliations

Jia-Rong Hou: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Yan-Hong Wang: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Ying-Nan Zhong: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Tong-Tong Che: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Yang Hu: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Jie Bao: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China
Ning Meng: Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, China

DOI: https://doi.org/10.3390/md19120712
Journal volume & issue: Vol. 19, no. 12
p. 712

Abstract

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Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

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