Protective effects of astragaloside IV on IL‑8‑treated diaphragmatic muscle cells

Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herbAstragalus membranaceus,which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the arteries from atherosclerosis; however the mechanisms underneath are unknown. The aim of this study was to investigate the effects of AsIV on blood lipids, CD40-CD40L signal system, and SDF-1/CXCR4 biological axis in high-fat diet apoE−/−mice and reveal the molecular mechanisms of AsIV against atherosclerosis. Here, we showed that AsIV alleviated the extent of atherosclerosis in aorta of apoE−/−mice. And AsIV can significantly downregulate PAC-1, CD40L, and CXCR4 expression on platelet surface in blood of high-fat diet apoE−/−mice. AsIV also can significantly downregulate mRNA and protein level of SDF-1 and CXCR4 in thoracic aorta. Consistent with aorta CXCR4 expression, CXCR4 in bone marrow-derived endothelial progenitor cell (EPC) was also reduced. Meanwhile biochemical analysis showed that AsIV could downregulate TG, TC, and LDL-C levels and upregulate HDL-C level in blood of high-fat diet apoE−/−mice. We concluded that the protective effects of AsIV in atherosclerosis injury may be related to regulating blood lipids, CD40-CD40L system, and SDF-1/CXCR4 biological axis. SDF-1/CXCR4 biological axis is probably one of the main targets of intervening atherosclerosis.

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The H2S-Donor Erucin Exhibits Protective Effects against Vascular Inflammation in Human Endothelial and Smooth Muscle Cells

Antioxidants ◽

10.3390/antiox10060961 ◽

2021 ◽

Vol 10 (6) ◽

pp. 961

Author(s):

Alma Martelli ◽

Eugenia Piragine ◽

Era Gorica ◽

Valentina Citi ◽

Lara Testai ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Cell Viability ◽

Caspase 3 ◽

Metabolic Diseases ◽

Vascular Inflammation ◽

Endothelial Permeability ◽

Muscle Cells ◽

Significant Inhibition ◽

Protective Effects

Preservation of vascular wall integrity against degenerative processes associated with ageing, fat-rich diet and metabolic diseases is a timely therapeutical challenge. The loss of endothelial function and integrity leads to cardiovascular diseases and multiorgan inflammation. The protective effects of the H2S-donor erucin, an isothiocyanate purified by Eruca sativa Mill. seeds, were evaluated on human endothelial and vascular smooth muscle cells. In particular, erucin actions were evaluated on cell viability, ROS, caspase 3/7, inflammatory markers levels and the endothelial hyperpermeability in an inflammatory model associated with high glucose concentrations (25 mM, HG). Erucin significantly prevented the HG-induced decrease in cell viability as well as the increase in ROS, caspase 3/7 activation, and TNF-α and IL-6 levels. Similarly, erucin suppressed COX-2 and NF-κB upregulation associated with HG exposure. Erucin also caused a significant inhibition of p22phox subunit expression in endothelial cells. In addition, erucin significantly prevented the HG-induced increase in endothelial permeability as also confirmed by the quantification of the specific markers VE-Cadherin and ZO-1. In conclusion, our results assess anti-inflammatory and antioxidant effects by erucin in vascular cells undergoing HG-induced inflammation and this protection parallels the preservation of endothelial barrier properties.

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Protective Effects of Astragaloside IV against LPS-Induced Endometritis in Mice through Inhibiting Activation of the NF-κB, p38 and JNK Signaling Pathways

Molecules ◽

10.3390/molecules24020373 ◽

2019 ◽

Vol 24 (2) ◽

pp. 373 ◽

Cited By ~ 8

Author(s):

Fengge Wang ◽

Shuxiong Chen ◽

Liang Deng ◽

Lu Chen ◽

Yuwen Huang ◽

...

Keyword(s):

Signaling Pathways ◽

Inflammatory Diseases ◽

Signal Pathways ◽

Protective Effects ◽

Astragaloside Iv ◽

Active Components ◽

Jnk Signaling ◽

Tnf Α ◽

Anti Inflammatory ◽

New Evidence

Endometritis, inflammation of the endometrium, is a common reproductive obstacle disease that can lead to infertility in female animals. Astragaloside IV (AS IV), one of the major and active components of the Astragalus membranaceus (Fisch.) Bunge, is known for its anti-inflammatory effects. In the present study, the effects and mechanisms of AS IV on lipopolysaccharide (LPS)-induced endometritis were investigated using a mouse model. Female mice were prepared with AS IV (0.01 mg/g) by gavage for six days before being stimulated with LPS. The results showed that the histopathological changes, levels of inflammatory cytokines (IL-1β and TNF-α), concentration of NO, and myeloperoxidase (MPO) activity in LPS-induced uteri were attenuated significantly by pretreatment with AS IV. Furthermore, LPS-induced activations of NF-κB, p38, and JNK signal pathways were suppressed by pretreatment with AS IV. In conclusion, the data provided new evidence that AS IV effectively attenuates LPS-induced endometritis through inhibition of TLR4-mediated NF-κB, p38, and JNK signaling pathways, implying that AS IV might become a promising potential anti-inflammatory agent for endometritis and other inflammatory diseases.

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Endothelial Cell Indoleamine 2, 3-Dioxygenase 1 Alters Cardiac Function Following Myocardial Infarction Through Kynurenine

Circulation ◽

10.1161/circulationaha.120.050301 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nada Joe Melhem ◽

Mouna Chajadine ◽

Ingrid Gomez ◽

Kiave-Yune Howangyin ◽

Marion Bouvet ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Smooth Muscle ◽

Endothelial Cell ◽

Cardiac Function ◽

Smooth Muscle Cells ◽

Ventricular Remodeling ◽

Muscle Cells ◽

Protective Effects ◽

Indoleamine 2

Background: Ischemic cardiovascular diseases, particularly acute myocardial infarction (MI) is one of the leading cause of mortality worldwide. Indoleamine 2, 3-dioxygenase 1 (IDO) catalyzes one rate-limiting step of L-Tryptophan (Trp) metabolism, and emerges as an important regulator of many pathological conditions. We hypothesized that IDO could play a key role to locally regulate cardiac homeostasis after MI. Methods: Cardiac repair was analyzed in mice harboring specific endothelial or smooth muscle cells or cardiomyocyte or myeloid cell deficiency of IDO and challenged with acute myocardial infarction. Results: We show that Kynurenine (Kyn) generation through IDO is markedly induced after MI in mice. Total genetic deletion or pharmacological inhibition of IDO limits cardiac injury and cardiac dysfunction after MI. Distinct loss of function of IDO in smooth muscle cells, inflammatory cells, or cardiomyocytes does not impact cardiac function and remodeling in infarcted mice. In sharp contrast, mice harboring endothelial cell-specific deletion of IDO show an improvement of cardiac function, as well as cardiomyocyte contractility and reduction in adverse ventricular remodeling. In vivo Kyn supplementation in IDO-deficient mice abrogates the protective effects of IDO deletion. Notably, Kyn precipitates cardiomyocyte apoptosis through reactive oxygen species production in an aryl hydrocarbon receptor-dependent mechanism. Conclusions: These data suggest that IDO could constitute a new therapeutic target during acute MI.

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