Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation

2019

Med Sci Monit

Background Endothelial injury is the main mechanism of atherosclerosis, and is caused by oxidized low-density lipoprotein (ox-LDL). Astragaloside IV (AS-IV) is the primary active ingredient of the Chinese herb Huangqi, and exhibits antioxidant and anti-inflammatory properties in cardiovascular diseases. This study investigated the protective effect of AS-IV in human umbilical vein endothelial cells (HUVECs). Material/Methods HUVEC cells were induced with ox-LDL to establish an in vitro atherosclerosis model. Then HUVECs were pretreated for 1 h with AS-IV at different concentrations (10, 20, and 50 μM) and then exposed to ox-LDL (100 μg/mL) for 48 h. The cell viability, lactate dehydrogenase (LDH) release, apoptosis, migration, intracellular reactive oxygen species (ROS), and NADPH oxidase activity of HUVECs were measured. qRT-PCR was performed to measure the mRNA expressions of Nrf2, HO-1, TNFα, and IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the supernatant contents of TNFα and IL-6. Results Exposure of HUVECs to ox-LDL reduced cell viability and migration, induced apoptosis, and increased intracellular ROS production and NADPH oxidase. Pretreatment with AS-IV (10, 20, and 50 μM) significantly enhanced the cell viability and migration, suppressed LDH release, apoptosis, ROS production, and NADPH oxidase in HUVECs, in a concentration-dependent manner. The AS-IV (50 μM) alone did not show significant differences from control. AS-IV increased mRNA expressions of Nrf2 and HO-1 and decreased mRNA expressions of TNFα and IL-6 in the ox-LDL-HUEVC cells. Furthermore, AS-IV reduced supernatant contents of TNFα and IL-6. Conclusions Astragaloside IV prevents ox-LDL-induced endothelial cell injury by reducing apoptosis, oxidative stress, and inflammatory response.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects Against Oxidized Low-Density Lipoprotein (ox-LDL)-Induced Endothelial Cell Injury by Reducing Oxidative Stress and Inflammation

Zhu

2019

Med Sci Monit

“…Mounting evidence suggests that the induction of HO-1 can ameliorate cell injury involved in atherogenesis. Zedoarondiol, an active compound extracted from Curcuma zedaria , has been reported to attenuate oxLDL-induced endothelial cell injury and inflammation via upregulation of HO-1 by Nrf2 [79]. Atractylenolide I (AO-I), isolated from Atractylodes macrocephala , inhibits ox-LDL-induced VSMCs migration and inflammatory responses partly in an HO-1-dependent manner [80].…”

Section: Atherosclerosismentioning

confidence: 99%

Heme, Heme Oxygenase, and Endoplasmic Reticulum Stress—A New Insight into the Pathophysiology of Vascular Diseases

Gáll

Balla

2019

IJMS

The prevalence of vascular disorders continues to rise worldwide. Parallel with that, new pathophysiological pathways have been discovered, providing possible remedies for prevention and therapy in vascular diseases. Growing evidence suggests that endoplasmic reticulum (ER) stress is involved in a number of vasculopathies, including atherosclerosis, vascular brain events, and diabetes. Heme, which is released from hemoglobin or other heme proteins, triggers various pathophysiological consequence, including heme stress as well as ER stress. The potentially toxic free heme is converted by heme oxygenases (HOs) into carbon monoxide (CO), iron, and biliverdin (BV), the latter of which is reduced to bilirubin (BR). Redox-active iron is oxidized and stored by ferritin, an iron sequestering protein which exhibits ferroxidase activity. In recent years, CO, BV, and BR have been shown to control cellular processes such as inflammation, apoptosis, and antioxidant defense. This review covers our current knowledge about how heme induced endoplasmic reticulum stress (HIERS) participates in the pathogenesis of vascular disorders and highlights recent discoveries in the molecular mechanisms of HO-mediated cytoprotection in heme stress and ER stress, as well as crosstalk between ER stress and HO-1. Furthermore, we focus on the translational potential of HIERS and heme oxygenase-1 (HO-1) in atherosclerosis, diabetes mellitus, and brain hemorrhage.

“…The cells were seeded in a 2 mL volume of media in six-well plates with and without stybenpropol A (12.5, 50, 200 μM) for 24 h, after which 12.5 ng/mL TNF-α was added at 37 °C for 12 h. The collected supernatants were assayed for VCAM-1, ICAM-1, IL-8, and IL-Iβ levels using appropriate ELISA kits, with absorbance at 450 nm measured via microplate reader [37,38].…”

Section: Methodsmentioning

confidence: 99%

Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells

Wang

et al. 2019

IJMS

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1β (IL-1β) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-β, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.