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. 2021 Feb 27:2021:6659240.
doi: 10.1155/2021/6659240. eCollection 2021.

Puerarin Attenuates LPS-Induced Inflammatory Responses and Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells through Mitochondrial Quality Control

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Puerarin Attenuates LPS-Induced Inflammatory Responses and Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells through Mitochondrial Quality Control

Xing Chang et al. Oxid Med Cell Longev. .

Retraction in

Abstract

Atherosclerosis is closely associated with the inflammatory reaction of vascular endothelial cells. Puerarin (Pue), the main active component isolated from the rhizome of Pueraria lobata, is an isoflavone compound with potent antioxidant properties. Although Pue exhibits promising antiatherosclerotic pharmacological effects, only a few studies have reported its protective effect on endothelial cells. This study found that Pue could partly regulate mitochondrial function in human umbilical vein endothelial cells (HUVECs) and reduce or inhibit lipopolysaccharide-induced inflammatory reactions and oxidative stress injury in HUVECs, likely via mitochondrial quality control. Furthermore, the protective effect of Pue on HUVECs was closely related to the SIRT-1 signaling pathway. Pue increased autophagy and mitochondrial antioxidant potential via increased SIRT-1 expression, reducing excessive production of ROS and inhibiting the expression of inflammatory factors and oxidative stress injury. Therefore, Pue may improve mitochondrial respiratory function and energy metabolism, increasing the vulnerability of HUVECs to an inflammatory state.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pue improves the activity of human umbilical vein endothelial cells (HUVECs) under LPS-induced inflammation. (a) Cell viability in an LPS-induced inflammatory state was determined using the CCK-8 method. After LPS stimulation, HUVEC viability was severely reduced. (b) HUVEC treatment with Pue at different concentrations (10, 20, 50, 100, and 150 mg/L). HUVEC viability under different drug concentrations was determined using the CCK-8 method. (c, d) HUVEC apoptosis level was analyzed before and after Pue administration. p < 0.05.
Figure 2
Figure 2
Pue inhibits LPS-induced inflammatory responses and oxidative stress damage in human umbilical vein endothelial cells (HUVECs). (a–f) Proinflammatory and anti-inflammatory factors and antioxidant enzymes were evaluated using ELISA. p < 0.05.
Figure 3
Figure 3
Pue improves mitochondrial activity under LPS-induced inflammation and oxidative stress damage. (a, f) HUVEC mitochondrial ROS expression. (d, e) Detection of mitochondrial membrane potential. (b, c) ELISA detection of mitochondrial respiratory complex I and III activity. p < 0.05.
Figure 4
Figure 4
Pue promotes mitochondrial energy metabolism in human umbilical vein endothelial cells (HUVECs) induced with LPS: (a) basic mitochondrial respiratory level; (b) maximum respiratory capacity; (c) spare respiratory capacity; (d) ATP production capacity; (e) nonmitochondrial oxygen respiration; (f) proton leakage level. p < 0.05.
Figure 5
Figure 5
Mechanism of Pue in regulating mitochondrial autophagy through SIRT-1. (a–e) Changes in transcription of atg3, atg7, sirt-1, and PINK1/parkin were determined by qPCR. p < 0.05. (f) Mitochondrial autophagy was observed with transmission electron microscopy. (g, h) Protein expression of Sirt-1, LC3-I\II, Beclin-1, and Bcl-2 was measured using western blotting. p < 0.05.
Figure 6
Figure 6
Inhibition of the SIRT-1 signaling pathway abolishes Pue-mediated protection. (a) CCK-8 analysis in different groups of human umbilical vein endothelial cells (HUVECs). (b–j) Enzyme-linked immunosorbent assays (ELISAs) showed antioxidant enzyme activities and anti-inflammatory factors in the different groups. (k) Laser confocal scanning was used to observe the alterations of myosin-VI in endothelial cells under Pue treatment. p < 0.05.

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