Biochanin A Mitigates Atherosclerosis by Inhibiting Lipid Accumulation and Inflammatory Response

Yu, Xiaohua; Chen, Jiaojiao; Deng, Wenyi; Xu, Xiaodan; Liu, Qi-Xian; Shi, Meng-Wen; Ren, Kewei

doi:10.1155/2020/8965047

Cited by 41 publications

(20 citation statements)

References 59 publications

(67 reference statements)

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“…In the previous reports, genistein had a hypolipidemic effect on menopausal women with hyperlipidemia [ 43 ] and ameliorated dyslipidemia and hepatic steatosis in hyperlipidemic hmsters [ 32 ] and diabetic mice [ 44 ]. Biochanin A mitigates dyslipidemia in hyperlipidemic mice [ 33 ], atherosclerotic mice [ 45 ], and diabetic rats [ 46 ]. In addition, tectorigenin and prunetin improved the effect of improving dyslipidemia in diabetic rats and obese mice, respectively [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

Hui

Hu²,

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. The aim of this study was to explore the hypolipidemic effect and mechanism of Dalbergia odorifera T. C. Chen leaf extract. Methods. The hypolipidemic effect of D. odorifera leaf extract was investigated using a hyperlipidemic rat model. Then, its mechanism was predicted using network pharmacology methods and verified using western blotting. Results. Compared with the levels in the model group, the serum levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) decreased significantly, whereas the serum level of high-density lipoprotein cholesterol (HDL-C) increased dramatically after treatment with the extract. The degrees of hepatocyte steatosis and inflammatory infiltration were markedly attenuated in vivo. Then, its hyperlipidemic mechanism was predicted using network pharmacology-based analysis. Thirty-five key targets, including sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-2 (SREBP-2), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), low-density lipoprotein receptor (LDLR), and ten signaling pathways, were associated with hyperlipidemia. Finally, it was verified that the extract downregulated the protein levels of SCAP, SREBP-2, and HMGCR, and upregulated protein levels of LDLR. Conclusion. These findings provided additional evidence of the hypolipidemic effect of D. odorifera leaf extract.

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Section: Discussionmentioning

confidence: 99%

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

Hui

Hu²,

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The uptake of Dil-ox-LDL by THP-1 macrophage-derived foam cells was performed as previously described [ 9 ]. In brief, THP-1 macrophage-derived foam cells were transfected with LV-Mock or LV-Asprosin for 72 h, washed twice with PBS, and then incubated with 10 μg/mL Dil-ox-LDL for 4 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…ABCA1- and ABCG1-dependent cholesterol efflux is the first and rate-limiting step of reverse cholesterol transport (RCT), a process by which excessive cholesterol in arterial wall cells is delivered by HDL to the liver for further metabolism and excretion [ 5 , 6 ]. Studies from our group and others have demonstrated that astragalin, C1q tumor necrosis factor-related protein 12, fargesin and biochanin A increase RCT efficiency and protect against atherosclerosis in apolipoprotein E-deficient (apoE −/− ) mice by up-regulating ABCA1 and ABCG1 expression [ 7 – 9 ]. Thus, searching for the novel mechanisms governing expression regulation of these two transporters is of critical importance to develop future therapeutic intervention in atherosclerotic cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

Asprosin inhibits macrophage lipid accumulation and reduces atherosclerotic burden by up-regulating ABCA1 and ABCG1 expression via the p38/Elk-1 pathway

Zou

Zhao

et al. 2022

J Transl Med

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Background Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive. Methods Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE−/− mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [3H]-labeled cholesterol. Results Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE−/− mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas. Conclusion Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE−/− mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.

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“…As reflected by the results of CCK-8 and scratch test (Figure 1E,1F, Figure S1A), ox-LDL strikingly enhanced cell viability and migration in VSMCs, whilst treatment with genistein markedly reduced the viability and migration of ox-LDL-exposed VSMCs. Uptake of large amounts of fat by VSMCs leads to cholesterol accumulation, which foams the cells, causing AS (20). Oil Red O staining (Figure 1G) demonstrated a dramatic increase of intracellular lipid particles in ox-LDL-exposed VSMCs and noticeable decline of intracellular lipid particles inox-LDL-exposed VSMCs following genistein treatment.…”

Section: Genistein Alleviated As In Rats and Inhibited Ox-ldlinduced ...mentioning

confidence: 99%

Anti-atherosclerotic effects of genistein in preventing ox-low-density lipoprotein-induced smooth muscle-derived foam cell formation via inhibiting SRC expression and L-Ca channel currents

Zhang¹,

Zhang²,

Zhang³

2022

Ann Transl Med

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Background: Atherosclerosis (AS) is associated with inflammation and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Genistein may curtail the migration of VSMCs.Therefore, explorations are required to determine the molecular mechanism of genistein in AS. In this context, animal and cell models were developed to ascertain mechanisms of genistein in AS by modulating VSMC activities. Methods: Genistein treatment and ectopic expression of lectin-like oxidized LDL receptor-1 (LOX-1) were conducted in high-fat diet-induced AS rats, followed by analyses of atherosclerotic plaque lesion areas and lipid deposition using Oil Red O and hematoxylin and eosin (HE) staining. The isolated VSMCs were stimulated with oxidized low-density lipoprotein (ox-LDL). Following genistein treatment combined with gain-and loss-of-function experiments in ox-LDL-exposed VSMCs, viability, migration, intracellular lipid deposition, intracellular cholesterol content, and L-type calcium (L-Ca) channel currents were assessed using Cell Counting Kit-8 (CCK-8), scratch test, Oil Red O staining, enzymatic colorimetry, and patchclamp experiments, respectively. Western blot analysis was performed to evaluate the protein expression of SRC proto-oncogene, non-receptor tyrosine kinase (SRC), calcium voltage-gated channel subunit alpha1 C (CACNA1C), and LOX-1. Results: Genistein treatment counteracted upregulated SRC phosphorylation, CACNA1C and LOX-1 expression, and L-Ca channel currents in aortic tissues of AS rats and ox-LDL-exposed VSMCs. Genistein deceased L-Ca channel currents by downregulating SRC, and SRC augmented LOX-1 expression by acting on the L-Ca channel subunit CACNA1C. The ox-LDL-induced VSMC proliferation, migration, and foaming of VSMCs were reduced by genistein treatment, silencing SRC, CACNA1C, or LOX-1, or suppressing L-Ca channels. Genistein treatment diminished atherosclerotic plaque lesion formation and lipid deposition, and these results were annulled by upregulating LOX-1. Conclusions: Collectively, genistein might block the SRC/CACNA1C/LOX-1 axis to impede ox-LDLinduced VSMC proliferation, migration, and foaming and alleviate AS formation.

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Biochanin A Mitigates Atherosclerosis by Inhibiting Lipid Accumulation and Inflammatory Response

Cited by 41 publications

References 59 publications

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

The Hypolipidemic Effect of Dalbergia odorifera T. C. Chen Leaf Extract on Hyperlipidemic Rats and Its Mechanism Investigation Based on Network Pharmacology

Asprosin inhibits macrophage lipid accumulation and reduces atherosclerotic burden by up-regulating ABCA1 and ABCG1 expression via the p38/Elk-1 pathway

Anti-atherosclerotic effects of genistein in preventing ox-low-density lipoprotein-induced smooth muscle-derived foam cell formation via inhibiting SRC expression and L-Ca channel currents

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