Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE<sup>-/-</sup> mice

Ma, Chuanrui; Xia, Ronglin; Yang, Shu; Liu, Lipei; Zhang, Jing; Feng, Ke; Shang, Yuna; Qu, Jingtian; Li, Lingwei; Chen, Ning; Xu, Shixin; Zhang, Wenwen; Mao, Jingyuan; Han, Jihong; Chen, Yuanli; Yang, Xiaoxiao; Duan, Yajun; Fan, Guanwei

doi:10.7150/thno.38115

Cited by 98 publications

(80 citation statements)

References 69 publications

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“…MOL000422 (kaempferol) can moderate cardiac injuries by inhibiting in ammatory responses and oxidative stress and mechanically linked to inhibition of nuclear factor-κB (NFκB) and nuclear factor-erythroid 2 p45-related factor-2 activation [35]. Moreover, during the animal experiment, MOL000392 (formononetin) can inhibit atherogenic monocyte adhesion and in ammation by regulating the interaction between KLF4 and SRA in ApoE de cient mice [36]. Besides, formononetin protected cardiomyocytes from oxygen-glucose deprivation/reoxygenation injury via inhibiting reactive oxygen species formation and promoting glycogen synthase kinase 3β phosphorylation [37].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Quan¹,

Miao²

2020

Preprint

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Background: Dilated cardiomyopathy (DCM) is a non-ischaemic cardiac muscle disease with structural and functional myocardial aberration can lead to extensive morbidity and mortality due to complications in particular heart failure and arrhythmia. Two classic Chinese medicine formulas, Shenfu decoction and Linguizhugan decoction, were both shown to exert therapeutic effects on heart disease. Thus, modified Shenfu and Linguizhugan decoction (SFLGZGD) is recommended for treatment DCM. However, its chemical and pharmacological characteristics remain to be elucidated. In the current study, a network pharmacology approach was applied to characterize the action mechanism and target genes of SFLGZGD on DCM.Methods: The gene expression of DCM was obtained from the Gene Expression Omnibus (GEO). All compounds were obtained from the correlative databases, and active mixture were selected according to their oral bioavailability (OB) and drug-likeness (DL) index. The potential targets of SFLGZGD were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database. The compound-target and target-pathway networks were constructed. The protein-protein interactive (PPI) network generated by R software was visualized by Cytoscape, and the topology scores, functional regions, and gene annotations were analyzed using plugins of Bisogenet and CytoNCA. The potential pathways related to target genes were determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.Results: A total of 963 differentially expressed genes (DEGs), including 538 upregulated genes and 425 downregulated, were obtained from GSE19303. A total of 636 ingredients in SFLGZGD were obtained, among which, 93 were chosen as bioactive components. The compound-target network included 10 bioactive components and 18 potential targets and a total of 1939 genes obtained in the PPI network, among them, a total of 16 genes were screened out. Moreover,129 terms on the GO analysis and six pathways obtained. Among these potential targets, EGFR, CDKN1A, MMP1, COL1A1, COL3A1, MMP3, ICAM1, and HSPB1 were identified as relatively high-degree targets.Conclusions: The network pharmacology-based approach in the current study has shown promising potential in identifying major therapeutic targets from TCM formulations. Besides, our study suggested that network pharmacology prediction may provide a useful tool for describing the molecular mechanism of SFLGZGD on DCM.

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Section: Discussionmentioning

confidence: 99%

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Quan¹,

Miao²

2020

Preprint

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“…The mice were daily checked for food intake, water drink and bodyweight gain during the treatment. At the end of experiment, all mice were anesthetized and euthanized as we previously reported [28,35], which was followed by collection of aortas, peritoneal macrophages, blood samples and other tissues. Serum was prepared to determine lipid pro le, including total cholesterol (Total-C, TC), high-density lipoprotein (HDL)-C, lowdensity lipoprotein (LDL)-C, and triglycerides (TG) [35].…”

Section: Animals and Treatment Schedulementioning

confidence: 99%

“…Foam cell formation in vitro and in vivo was determined by Oil Red O staining as described [28,37]. In vivo, peritoneal macrophage were isolated from TFA-treated apoE −/− mice and seeded on cover slips in 24-well plates, and then stained with Oil Red O solution.…”

Section: Determination Of Foam Cell Formation In Vitro and In Vivomentioning

confidence: 99%

“…Macrophage were incubated in medium containing DiI-oxLDL or 3-dodecanoyl-NBD cholesterol to evaluate ability of cholesterol uptake and e ux as previously studied [28]. Brie y, in 12-well plates, macrophages (1.0 × 10 6 cells/well) pretreated with TFA at different doses were incubated with 10 µg/mL Dil-oxLDL (Introvegen) in RPMI 1640 at 37 °C for 6 h. Fluorescence intensity was examined by a uorescence microscopy.…”

Section: Cholesterol Uptake and E Ux Assaymentioning

confidence: 99%

“…Formononetin, as a component of Astragalus avone, can protect against obesity that has been de ned as an atherogenic contributor [25][26][27]. Furthermore, formononetin can inhibit foam cell formation [28];…”

Section: Introductionmentioning

confidence: 99%

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Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via improving lipid metabolism and inhibition of inflammation in apoE-/- mice

Zhang

Yang

et al. 2020

Preprint

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Background: Atherosclerosis is a major pathogenic factor in cardiovascular diseases during the aging process. Foam cell formation and endothelial dysfunction play a key role in the initiation and development of atherosclerosis, which are affected by lipid disorder and inflammation. Therefore, the drug for inhibition of endothelial dysfunction and the subsequent foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from Astragalus membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. Methods: In this study, we determined whether TFA could inhibit atherosclerosis; and uncovered the underlying molecular mechanisms. In vivo, apoE deficient mice were treated with TFA contained in high-fat diet for 16 weeks. After treatment, aorta, macrophage and serum samples were collected to determine atherosclerotic lesions, lipid metabolism, and expression of associated genes. Concurrently, we investigated the effect of TFA on monocyte adhesion, foam cell formation, endothelial activation, and macrophage polarization in vitro and in vivo. Results: TFA reduced atherosclerotic plaque size; and enhanced lesion stability by changing the composition of plaque. Moreover, foam cell formation and its accumulation in arterial wall were attenuated by TFA, which might be attributed to improved lipid disorder, reduced inflammation, and decreased monocyte adhesion to endothelial cells. Mechanistically, TFA reduced the expression of scavenger receptor, such as CD36 and SRA; promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced the expression of miR-33, a negative regulator of cholesterol efflux as well as positive mediator on inflammation; and concurrently reduced NFkB activity, by which de-repressed ABCA1/G1 activity and inhibited the inflammation. Conclusions: This study demonstrates that TFA can attenuate atherosclerosis via dual inactivation of miR-33 and NFkB signaling pathway and inhibition of scavenger receptors (CD36 and SRA), which suggests that TFA might be a novel therapeutic approach for inhibition of atherosclerosis.

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Pax‐8: Molecular biology, pathophysiology, and potential pathogenesis

Zhou,

Li,

Cheng

et al. 2023

BioFactors

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Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax‐8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax‐8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax‐8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax‐8 to provide a new research direction for Pax‐8.

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Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE^-/- mice

Cited by 98 publications

References 69 publications

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via improving lipid metabolism and inhibition of inflammation in apoE-/- mice

Pax‐8: Molecular biology, pathophysiology, and potential pathogenesis

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Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- mice

Cited by 98 publications

References 69 publications

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Exploring the Pharmacological Mechanism of the modified Chinese medicine formulas “Shenfu-Linguizhugan decoction” treating Dilated cardiomyopathy Based on Network Pharmacology

Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via improving lipid metabolism and inhibition of inflammation in apoE-/- mice

Pax‐8: Molecular biology, pathophysiology, and potential pathogenesis

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Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE^-/- mice