Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats

Wang, Feng Ling; Tang, Liyuan; Yang, Feng; La, Zhu; Cai, Ming; Wei, Wei

doi:10.1007/s11033-012-2321-5

Cited by 45 publications

(32 citation statements)

References 51 publications

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“…15,39 In the present study we evaluated the renoprotective effect of BBR in DN and found that treatment of DN rats with 100 and 200 mg/kg BBR for 6 weeks significantly increased renal β-arrestin 1 and β-arrestin 2 expression in DN rats. Together with findings from previous studies, 40 these observations lead us to conclude that βarrestin 1 and β-arrestin 2 levels are negatively correlated with ICAM-1 and VCAM-1 expression. Together, the results indicate that BBR has desirable protective effects on the kidney, which are likely related to the downregulation of ICAM-1 and VCAM-1 expression and upregulation of β-arrestin 1 and β-arrestin 2 in the kidneys of DN rats.…”

Section: Discussionsupporting

confidence: 83%

Renoprotective effects of berberine and its potential effect on the expression of β‐arrestins and intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in streptozocin‐diabetic nephropathy rats

Tang

Cai

et al. 2015

Journal of Diabetes

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Background: Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of β-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. Methods: To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of β-arrestin 1 and β-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. Results: Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in β-arrestin 1 and β-arrestin 2. Conclusions: Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney.

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Section: Discussionsupporting

confidence: 83%

Renoprotective effects of berberine and its potential effect on the expression of β‐arrestins and intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in streptozocin‐diabetic nephropathy rats

Tang

Cai

et al. 2015

Journal of Diabetes

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“…Analysis of the diabetes complication control trial showed that hypercholesterolemia is associated with an increased albumin excretion rate (40). Experimental animal models using mice, rats, and pigs have shown that high-fat feeding to diabetic animals is associated with accelerated development of albuminuria, mesangial matrix expansion, and glomerular hypertrophy (41)(42)(43)(44). Although the mechanism is unknown, studies have shown that increased oxidized low density lipoprotein induces podocyte retraction and albumin permeability (45).…”

Section: Discussionmentioning

confidence: 99%

Blocking Ligand Occupancy of the αVβ3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs

et al. 2014

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Hyperglycemia stimulates secretion of αVβ3 ligands from vascular cells, including endothelial cells, resulting in activation of the αVβ3 integrin. This study determined whether blocking ligand occupancy of αVβ3 would inhibit the development of diabetic nephropathy. Ten diabetic pigs received an F(ab)2 fragment of an antibody directed against the extracellular domain of the β3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 μg of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 μg/mg), whereas diabetic animals treated with the anti-β3 F(ab)2 excreted 119 ± 55 μg/mg (P < .05). Mesangial volume/glomerular volume increased to 21 ± 2.4% in control-treated diabetic animals compared with 14 ± 2.8% (P < .01) in animals treated with active antibody. Diabetic animals treated with control F(ab)2 had significantly less glomerular podocin staining compared with nondiabetic animals, and this decrease was attenuated by treatment with anti-β3 F(ab)2. Glomerular basement membrane thickness was increased in the control, F(ab)2-treated diabetic animals (212 ± 14 nm) compared with nondiabetic animals (170 ± 8.8 nm), but it was unchanged (159.9 ± 16.4 nm) in animals receiving anti-β3 F(ab)2. Podocyte foot process width was greater in control, F(ab)2-treated, animals (502 ± 34 nm) compared with animals treated with the anti-β3 F(ab)2 (357 ± 47 nm, P < .05). Renal β3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-β3-treated group. We conclude that administration of an antibody that inhibits activation of the β3-subunit of αVβ3 that is induced by hyperglycemia attenuates proteinuria and early histologic changes of diabetic nephropathy, suggesting that it may have utility in preventing the progression of this disease complication.

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“…In recent years, BBR has been widely used to treat diabetes and its complications 23,24. BBR treatment may restore the renal functional parameters, improve the glucose and lipid metabolism disorders, and suppress alterations of histologic and ultrastructural changes in the kidney 25. Moreover, BBR inhibits mesangial cell proliferation and extracellular matrix accumulation induced by high glucose (HG) and ameliorates tubulointerstitial fibrosis in DN, which suggests that BBR can be used as a potential drug for DN 26–30.…”

Section: Introductionmentioning

confidence: 99%

Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

Yang

Zhao

Zhang

et al. 2017

DDDT

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Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

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Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats

Cited by 45 publications

References 51 publications

Renoprotective effects of berberine and its potential effect on the expression of β‐arrestins and intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in streptozocin‐diabetic nephropathy rats

Renoprotective effects of berberine and its potential effect on the expression of β‐arrestins and intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 in streptozocin‐diabetic nephropathy rats

Blocking Ligand Occupancy of the αVβ3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs

Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

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