Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2

Wang, Yaozhen; Fu, Wenwen; Xue, Yong; Lu, Zeyuan; Li, Yuangeng; Yu, Ping; Yu, Xiaofeng; Xu, Huali; Sui, Dayun

doi:10.3389/fphar.2021.620524

Cited by 17 publications

(18 citation statements)

References 96 publications

(116 reference statements)

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“…We characterized HUVEC for the expression of the typical endothelial markers ( Supplementary Figure S1 ), confirming the presence of CD31, CD105, CD146, CD54, VEGFR-2 endothelial markers and not of CD45 [ 26 , 27 , 28 , 29 ]. Moreover, we confirmed the ACE2 (spike receptor) expression by HUVEC, as demonstrated by previous studies [ 30 , 31 , 32 ] using cytofluorimetric analysis ( Supplementary Figure S1 ). Therefore, we analyzed the possible interaction of S-EVs with target cells.…”

Section: Resultssupporting

confidence: 89%

Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Verta

Grange

Škovroňová

et al. 2022

Cells

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Extracellular vesicles (EVs) and viruses share common features: size, structure, biogenesis and uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs), we collected EVs from SARS-CoV-2 spike expressing human embryonic kidney (HEK-293T) cells by stable transfection with a vector coding for the S1 and S2 subunits. S-EVs were characterized using nanoparticle tracking analysis, ExoView and super-resolution microscopy. We obtained a population of EVs of 50 to 200 nm in size. Spike expressing EVs represented around 40% of the total EV population and co-expressed spike protein with tetraspanins on the surfaces of EVs. We subsequently used ACE2-positive endothelial and bronchial epithelial cells for assessing the internalization of labeled S-EVs using a cytofluorimetric analysis. Internalization of S-EVs was higher than that of control EVs from non-transfected cells. Moreover, S-EV uptake was significantly decreased by anti-ACE2 antibody pre-treatment. Furthermore, colchicine, a drug currently used in clinical trials, significantly reduced S-EV entry into the cells. S-EVs represent a simple, safe, and scalable model to study host-virus interactions and the mechanisms of novel therapeutic drugs.

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Section: Resultssupporting

confidence: 89%

Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Verta

Grange

Škovroňová

et al. 2022

Cells

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“…Recently, a number of traditional herbal medicines have been identified to have antidiabetic properties in T2DM ( 29 ). Ginsenoside Rg1 ( 30 ), Rc ( 31 ), Rk3 ( 32 ), and Rb1 ( 33 ) are able to repress endothelial and pancreatic β-cell apoptosis and inflammation and are beneficial in preventing diabetic complications, such as diabetic nephropathy and retinopathy. Active ingredients extracted from Astragalus membranaceus , including baicalin, baicalein, and wogonin, relieved high glucose-induced endothelial inflammation to prevent and treat diabetic complications ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

Lei¹,

Sun²,

Liu³

et al. 2022

Ann Transl Med

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Background: Bergenin, an active constituent of plants of the genus Bergenia, has been reported to have antidiabetic properties. This study investigated whether bergenin is beneficial for treating type 2 diabetes mellitus (T2DM) via regulating NOD-like receptor family-pyrin domain containing 3 (NLRP3) inflammasome.Methods: Two pancreatic β-cell lines, INS-1 and MIN6, were treated with 1, 3, or 10 μM bergenin in the absence or presence of palmitic acid (PA). Cell Counting Kit (CCK)-8, flow cytometry, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescent staining were performed.Results: Bergenin with concentrations of 1, 3, and 10 μM had no cytotoxicity in INS-1 and MIN6 cells.However, bergenin dose-dependently relieved PA-induced pancreatic β-cell loss and apoptosis. Bergenin dose-dependently inhibited NLRP3 inflammasome-related inflammation, as observed by the downregulation of NLRP3, apoptosis associated speck like protein (ASC), cleaved caspase-1, and gasdermin-D (GSDMD)-N, as well as the decreased release of cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, and IL-18. The NOD-like receptor signaling pathway was predicted to be a downstream signaling pathway regulated by bergenin. Autodock Vina software docked bergenin with NLRP3. The binding energy of interaction was −5.101 kcal/mol and the root-mean-square deviation (RMSD) score was 1.5901A. Treating pancreatic β-cells with bergenin accelerated the degeneration of NLRP3. Furthermore, restoration of NLRP3 expression using plasmid transfection reversed the protective effects of bergenin on pancreatic β-cells.Conclusions: Our data suggests that bergenin is a potential agent for treating T2DM through preventing NLRP3 inflammasome-related inflammation in pancreatic β-cells.

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“…Endothelial cells (EC) from human aorta (TeloHAEC cell line, CRL-4052) were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA) and grown as a monolayer, at 37 °C under a humidified atmosphere with 5% CO 2 , in Vascular Cell Basal Medium (PCS-100-030, ATCC, Manassas, VA, USA) supplemented with Endothelial Cell Growth kit-VEGF (PCS-100-041, ATCC, Manassas, VA, USA). To induce insulin-resistance (IR), EC were exposed to palmitic acid (PA) up to 1.5 mM for 24 and 48 h. To confirm the IR assessment, the 48 h treatment with PA was followed by incubation with 100 nM recombinant human insulin (91077C, Merck KGaA, Darmstadt, Germany) for 30 min, as previously described [ 26 ]. δ-Valerobetaine (δVB) synthesis and purification were carried out as previously described [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

et al. 2022

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Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p < 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p < 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3+) suppressed the PA-induced autophagy (mimic NC+PA) (p < 0.01), inflammation, and pyroptosis (p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries.

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Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2

Cited by 17 publications

References 96 publications

Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Bergenin inhibits palmitic acid-induced pancreatic β-cell inflammatory death via regulating NLRP3 inflammasome activation

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

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