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Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway.

ABSTRACT: Background:Aloe emodin (AE) is a lipid-lowering agent, which could be used to treat hyperlipidemia, thereby reducing the risk of cardiovascular disease. Recent evidence suggests that hyperlipidemia is associated with many cardiac pathological alterations and might worsen myocardial damages. Purpose:The purpose of this study is to evaluate the potential roles and mechanisms of AE in hyperlipidemia-induced oxidative stress and inflammation in the heart. Study Design. We established a hyperlipidemia-induced cardiac inflammation model in rats and cells then administered AE and observed its effect on hyperlipidemia-induced cardiac inflammation. Methods:We used a mouse model of hyperlipidemia caused by a high-fat diet (HFD) for 10 weeks and cell culture experimental models of inflammation in the heart stimulated by PA for 14?h. Inflammatory markers were detected by qRT-PCR, WB, and immunofluorescence. Results:We demonstrated that the expression levels of proinflammatory cytokines IL-1?, IL-6, and TNF-? were increased in the HFD group compared to the normal diet (ND) group, whereas AE treatment significantly reduced their levels in the myocardium. In addition, vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM-1) protein expressions were also inhibited by AE. Our in vitro study showed AE treatment dose-dependently decreased the expression of IL-1?, IL-6, and TNF-? were increased in the HFD group compared to the normal diet (ND) group, whereas AE treatment significantly reduced their levels in the myocardium. In addition, vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM-1) protein expressions were also inhibited by AE. Our ?B, and p-P65l in vivo and in vitro study showed AE treatment dose-dependently decreased the expression of IL-1. Conclusion:Taken together, our findings disclose that AE could alleviate HFD/PA-induced cardiac inflammation via inhibition of the TLR4/NF-?B signaling pathway. Thus, AE may be a promising therapeutic strategy for preventing hyperlipidemia-induced myocardial injury.?B, and p-P65l.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7025072 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway.

Chen Yingfu Y Feng Burong B Yuan Ye Y Hu Juan J Zhao Wei W Jiang Huiwei H Li Wen W Fan Ziyi Z Du Zhimin Z

Mediators of inflammation 20200205

<h4>Background</h4>Aloe emodin (AE) is a lipid-lowering agent, which could be used to treat hyperlipidemia, thereby reducing the risk of cardiovascular disease. Recent evidence suggests that hyperlipidemia is associated with many cardiac pathological alterations and might worsen myocardial damages.<h4>Purpose</h4>The purpose of this study is to evaluate the potential roles and mechanisms of AE in hyperlipidemia-induced oxidative stress and inflammation in the heart. <i>Study Design</i>. We estab ...[more]

PMID: 32089647

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Project description:Aloe arborescens is a relevant species largely used in traditional medicine of several countries. In particular, the decoction of leaves is prepared for various medicinal purposes including antidiabetic care. The aim of this research was the study of the antiglycation activity of two A. arborescens leaf extracts and isolated compounds: aloin and aloe-emodin. These phytoconstituents were quantitatively assessed in methanolic and hydroalcoholic extracts using high performance liquid chromatography (HPLC) analysis. In addition, the total phenolic and flavonoid contents were detected. In order to study their potential use in diabetic conditions, the antiglycation and antiradical properties of the two extracts and aloin and aloe-emodin were investigated by means of bovine serum albumin (BSA) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays; further, their cytotoxicity in HT-29 human colon adenocarcinoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, the ability of aloin and aloe-emodin to permeate the cellular membranes of HT-29 cells was determined in order to estimate their potential in vivo absorption. This assessment indicated that aloe-emodin can substantially pass through cell membranes (~20%), whereas aloin did not permeate into HT-29 cells. Overall, the data show that both the methanolic and the hydroalcoholic A. arborescens extracts determine significant inhibition of glycation and free-radical persistence, without any cytotoxic activity. The data also show that the antiglycation and the antiradical activities of aloin and aloe-emodin are lower than those of the two extracts. In relation to the permeability study, only aloe-emodin is able to cross HT-29 cellular membranes, showing the attitude to pass through the intestinal layer. Overall, the present data surely support the traditional use of A. arborescens leaf extracts against hyperglycemic conditions, while aloin and aloe-emodin as potential drugs need further study.

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Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway.

Publications

Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway.

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