Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs.

Abstract

Endothelial dysfunction plays important roles in vascular dysfunction under diabetic conditions. The generation of advanced glycation end products (AGEs), which can induce inflammation and oxidative stress, is pivotal in endothelial dysfunction. Salidroside, a major active compound in Rhodiola rosea, exerts protective effects against vascular diseases. To study the effects and mechanism of salidroside in diabetes-induced vascular endothelial dysfunction, an in vitro model was established with AGEs-induced human umbilical vein endothelial cells (HUVECs). Then, cell viability, cell apoptosis, pro-inflammatory cytokines and oxidative biomarkers were tested to determine the effects of salidroside at 10, 50 and 100 μM doses on AGEs induced HUVECs. Additionally, RNA-Seq and bioinformatics analyses were used to search for the underlying mechanism of salidroside. The results showed that salidroside promoted cell viability and significantly alleviated cell apoptosis in AGEs-induced HUVECs. Furthermore, salidroside remarkably decreased the levels of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and impeded the expression of VCAM-1 and ICAM-1 induced by AGEs. Additionally, salidroside promoted superoxide dismutase (SOD) activity and increased catalase (CAT) and glutathione peroxidase (GSH-Px) levels while inhibiting the intracellular generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in AGEs-induced HUVECs. Importantly, salidroside alleviated endothelial inflammation and oxidative stress by activating AMPK phosphorylation and inhibiting NF-ĸB p65 and NLRP3 inflammasome activation. Therefore, we used compound C, an accepted AMPK inhibitor, to further demonstrate the mechanism. Interestingly, the phenomenon produced by salidroside was abolished. Our findings suggest that salidroside ameliorates AGEs-induced endothelial inflammation and oxidative stress, partially via the AMPK/NF-κB/NLRP3 signaling pathway.

• Authors: Rong Hu, Ming-Qing Wang, Shi-Hao Ni, Ming Wang, Ling-Yu Liu, Hai-Yan You, Xiao-Hui Wu, Yan-Jing Wang, Lu Lu, Lian-Bo Wei
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 867 Pg. 172797 (Jan 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 31747547 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Glucosides
• Glycation End Products, Advanced
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Phenols
• RELA protein, human
• Reactive Oxygen Species
• Transcription Factor RelA
• AMP-Activated Protein Kinases
• rhodioloside

Topics

• AMP-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Cell Line
• Diabetic Angiopathies (drug therapy, immunology, metabolism)
• Endothelium, Vascular (cytology, drug effects, immunology, metabolism)
• Glucosides (pharmacology, therapeutic use)
• Glycation End Products, Advanced (immunology, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, immunology, metabolism)
• Humans
• Inflammasomes (antagonists & inhibitors, immunology, metabolism)
• Inflammation (drug therapy, immunology, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (immunology, metabolism)
• Oxidative Stress (drug effects, immunology)
• Phenols (pharmacology, therapeutic use)
• RNA-Seq
• Reactive Oxygen Species (immunology, metabolism)
• Signal Transduction (drug effects, immunology)
• Transcription Factor RelA (immunology, metabolism)