Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1

Ren, Kewei; Li, Heng; Zhou, Hongyu; Liang, Yin; Tong, Min; Chen, Lu; Zheng, Xi-Long; Zhao, Guo-Jun

doi:10.18632/aging.102498

Cited by 57 publications

(36 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ABCA1 and ABCG1 had similar function on cholesterol e ux (29). ABCG1 also exerted anti-in ammatory effects on in ammatory macrophage foam cells (30). ABCG1 knockout mice might increase the in ltration of in ammatory cells in atherosclerosis.…”

Section: Discussionmentioning

confidence: 95%

The Mechanism Study of Xiao-Xian-Xiong Decoction in the Treatment of Atherosclerosis with Network Pharmacology

Xiao¹,

Li²,

Fan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Xiao-Xian-Xiong decoction is a useful formula in the treatment of atherosclerosis in traditional Chinese medicine. In this study, we aimed to investigate the function of Xiao-Xian-Xiong decoction in the treatment of atherosclerosis. Methods: In this study, we conducted the method of network pharmacology and molecular docking to discover the mechanism of Xiao-Xian-Xiong decoction against atherosclerosis. Then, we validated the function of Xiao-Xian-Xiong decoction in atherosclerosis in vitro. We investigated the function and mechanism of Xiao-Xian-Xiong decoction in RAW264.7 macrophage-derived foam cells.Results: We identified 213 targets of Xiao-Xian-Xiong decoction and 331 targets of atherosclerosis. The PPI networks of Xiao-Xian-Xiong decoction and atherosclerosis were constructed. Furthermore, the two PPI networks were merged and the core PPI network was obtained. Then, functional enrichment analysis was conducted with GO and KEGG signaling pathway analysis. KEGG analysis indicated Xiao-Xian-Xiong decoction was correlated with ubiquitin mediated proteolysis pathway, PI3K-AKT pathway, MAPK pathway, Notch signaling pathway, and TGF-β signaling pathway. At last, we validated the function of Xiao-Xian-Xiong decoction with atherosclerosis in vitro. Xiao-Xian-Xiong decoction reduced lipid accumulation and promoted the outflow of cholesterol in RAW264.7-derived foam cells. Xiao-Xian-Xiong decoction increased the expression of ABCA1 and ABCG1 protein in foam cells. ABCA1 and ABCG1 were related with regulation of the inflammatory pathway and cell proliferation in atherosclerosis.Conclusions: Combined the mechanism of available treatments of atherosclerosis, we inferred Xiao-Xian-Xiong decoction could alleviate atherosclerosis by inhibiting inflammatory response and cell proliferation.

show abstract

Section: Discussionmentioning

confidence: 95%

The Mechanism Study of Xiao-Xian-Xiong Decoction in the Treatment of Atherosclerosis with Network Pharmacology

Xiao¹,

Li²,

Fan³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It is estimated that they are responsible for~70% of cholesterol release from lipid-loaded macrophages 43 . Our groups and others have revealed that administration of fargesin, mangiferin, or polydatin inhibits macrophage lipid accumulation and atherosclerotic plaque formation by facilitating ABCA1-and ABCG1dependent cholesterol efflux 6,35,44 . SR-A and CD36 are the members of the scavenger receptor family and account for 75-90% of ox-LDL internalization by macrophages 45 .…”

Section: Discussionmentioning

confidence: 96%

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

C1q tumor necrosis factor-related protein 12 (CTRP12), a conserved paralog of adiponectin, is closely associated with cardiovascular disease. However, little is known about its role in atherogenesis. The aim of this study was to examine the influence of CTRP12 on atherosclerosis and explore the underlying mechanisms. Our results showed that lentivirus-mediated CTRP12 overexpression inhibited lipid accumulation and inflammatory response in lipid-laden macrophages. Mechanistically, CTRP12 decreased miR-155-5p levels and then increased its target gene liver X receptor α (LXRα) expression, which increased ATP binding cassette transporter A1 (ABCA1)- and ABCG1-dependent cholesterol efflux and promoted macrophage polarization to the M2 phenotype. Injection of lentiviral vector expressing CTRP12 decreased atherosclerotic lesion area, elevated plasma high-density lipoprotein cholesterol levels, promoted reverse cholesterol transport (RCT), and alleviated inflammatory response in apolipoprotein E-deficient (apoE−/−) mice fed a Western diet. Similar to the findings of in vitro experiments, CTRP12 overexpression diminished miR-155-5p levels but increased LXRα, ABCA1, and ABCG1 expression in the aortas of apoE−/− mice. Taken together, these results suggest that CTRP12 protects against atherosclerosis by enhancing RCT efficiency and mitigating vascular inflammation via the miR-155-5p/LXRα pathway. Stimulating CTRP12 production could be a novel approach for reducing atherosclerosis.

show abstract

“…Cholesterol content in foam cells is modulated by a complex mechanism of ox‐LDL internalization and excess cholesterol effusion (Zhao et al., 2016). Accumulating evidence has indicated that active ingredients from plants such as kuwanon G and mangiferin inhibit the formation of macrophage‐derived foam cells via the promotion of the LXRα–ABCA1/ABCG1‐mediated cholesterol efflux pathway (Liu et al., 2018; Ren et al., 2019). In accordance with the in vivo results, the increase in the expression of LXRα, ABCA1 and ABCG1 by danthron was confirmed in vitro .…”

Section: Discussionmentioning

confidence: 99%

Danthron attenuates experimental atherosclerosis by targeting foam cell formation

Shi

Zhang

Lin

et al. 2021

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the central question of this study?Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells? What are the main findings and their importance?Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE−/− mice. Danthron inhibited foam cell formation in oxidized low‐density lipoprotein‐induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP‐activated protein kinase–sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis. Abstract Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro. This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE−/− mice were fed a high‐fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low‐density lipoprotein (ox‐LDL, 50 μg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP‐activated protein kinase (AMPK) inhibitor compound C was added to ox‐LDL‐stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP‐binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK–sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox‐LDL‐induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK–SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro. Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK–SIRT1 signalling pathway.

show abstract

Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1

Cited by 57 publications

References 49 publications

The Mechanism Study of Xiao-Xian-Xiong Decoction in the Treatment of Atherosclerosis with Network Pharmacology

The Mechanism Study of Xiao-Xian-Xiong Decoction in the Treatment of Atherosclerosis with Network Pharmacology

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway

Danthron attenuates experimental atherosclerosis by targeting foam cell formation

Contact Info

Product

Resources

About