Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.

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“…In diabetic mice: reduced endothelia damage through lipotoxicity, improved insulin sensitivity, attenuated Mϕ-induced inflammation [57]…”

Section: Reduces Mϕ Infiltration and M1 Polarizationmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

150

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“…The protective roles of natural compounds in renal diseases have been discussed previously. For example, tectorigenin has been reported to alleviate diabetic nephropathy via regulating the AdipoR1/2 signaling; magnesium lithospermate B was able to exert renal protective roles via suppressing the mitochondrial pathway of apoptosis 10) ; astragaloside IV was shown to inhibit the epithelial-mesenchymal transition of podocytes that induced by glucose through regulating the SIRT-NF-κB p65 signaling 21) . Calycosin has been reported as an alternative medication for the treatment of some diseases e.g.…”

Section: Biological and Pharmaceutical Bulletin Advance Publicationmentioning

confidence: 99%

“…Ang Ⅱ was reported to participate in different biological processes, for example, cell growth, fibrosis, and immune reactions. Increased expression of Ang II can lead to increased growth ability and decreased apoptosis of the glomerular mesangial cells, which was considered as an important reason for the incidence and progress of TIF 1,10) .…”

Section: Introductionmentioning

confidence: 99%

Calycosin may Alleviate Ang II-Induced Pro-proliferative Effects on Glomerular Mesangial Cells <i>via</i> Partially Inhibiting Autophagy and ERK Signaling Pathway

Ding

Luan

et al. 2020

Biological & Pharmaceutical Bulletin

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Over-expression of angiotensin II (Ang II) is an important reason for the development of chronic kidney disease. Calycosin is the active component of traditional Chinese medicine astragali radix. The present work aims to explore whether calycosin could affect the growth and apoptosis ability of the Ang II treated glomerular mesangial cells and the underlying mechanism. Human glomerular mesangial cells (GMCs) were cultured and treated by Ang II and 0, 0.1, 1 or 10 μM calycosin, and the viability and proliferation of the cells were determined by MTT and EdU staining; moreover, the apoptosis of the cells was examined by flow cytometry assay; furthermore, the expression levels of ERK, pERK , anti-apoptotic factor Bcl-2, as well as pro-apoptotic factor Bax have been examined by western blot methods; finally, the expression of autophagic markers in each group was examined by WB and immunocytochemistry methods. We found that Ang II increased viability and proliferation, meanwhile inhibited apoptosis of the GMCs; furthermore, 1 and 10 μM calycosin significantly inhibited the growth and promoted the apoptosis of the GMCs treated by Ang II; moreover, calycosin also inhibited ERK signaling in mesangial cells activated by Ang II treatment; Finally, calycosin could inhibit Ang II induced autophagy of GMCs in a dose-dependent manner. In conclusion, calycosin may alleviate Ang II-induced pro-proliferative and anti-apoptotic effects on glomerular mesangial cells at least partially via inhibiting autophagy and ERK signaling pathway, suggesting that calycosin may function as a potential alternative medication for the management of chronic kidney diseases.

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“…Western Blot And Quantitative Real-time PCR Total cellular proteins were extracted from cells or liver tissue. Protein expression of ABCA1, ABCG1, CD36, GAPDH, FASN, SREBP1c, SRBI, IκBα, pi-IκBα, p65, pi-p65, and SRA were determined by Western blot as previously reported [38]. Total RNA was isolated and puri ed, and cDNA was synthesized from 1 mg of total RNA using a reverse transcription kit (Vazyme bioteck co., ltd).…”

Section: Cholesterol Uptake and E Ux Assaymentioning

confidence: 99%

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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Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway

Cited by 51 publications

References 55 publications

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calycosin may Alleviate Ang II-Induced Pro-proliferative Effects on Glomerular Mesangial Cells <i>via</i> Partially Inhibiting Autophagy and ERK Signaling Pathway

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

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