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. 2020 Oct 8:14:4135-4148.
doi: 10.2147/DDDT.S274256. eCollection 2020.

Wogonin Ameliorates Renal Inflammation and Fibrosis by Inhibiting NF-κB and TGF-β1/Smad3 Signaling Pathways in Diabetic Nephropathy

Zhi-Chao Zheng  1 , Wei Zhu  1 , Lei Lei  1 , Xue-Qi Liu  1 , Yong-Gui Wu  1
Affiliations

Wogonin Ameliorates Renal Inflammation and Fibrosis by Inhibiting NF-κB and TGF-β1/Smad3 Signaling Pathways in Diabetic Nephropathy

Zhi-Chao Zheng et al. Drug Des Devel Ther. .

Abstract

Introduction: Diabetic nephropathy (DN) has become an increasing threat to health, and inflammation and fibrosis play important roles in its progression. Wogonin, a flavonoid, has been proven to suppress inflammation and fibrosis in various diseases, including acute kidney injury. This study aimed at investigating the effect of wogonin on diabetes-induced renal inflammation and fibrosis.

Materials and methods: Streptozotocin (STZ)-induced diabetic mouse models received gavage doses of wogonin (10, 20, and 40 mg/kg) for 12 weeks. Metabolic indices from blood and urine and pathological damage of glomerulus in the diabetic model were assessed. Glomerular mesangial cells SV40 were cultured in high glucose (HG) medium containing wogonin at concentrations of 1.5825, 3.125, and 6.25 μg/mL for 24 h. Inflammation and fibrosis indices were evaluated by histopathological, Western blotting, and PCR analyses.

Results: Wogonin treatment ameliorated albuminuria and histopathological lesions in diabetic mice. Inflammatory cytokines, such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and related signaling pathway NF-κB were downregulated after the administration of wogonin in vivo and in vitro. Furthermore, wogonin reduced the expression of extracellular matrix (ECM), including fibronectin (FN), collagen IV (Col-IV), α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in the kidneys of diabetic mice and HG-induced mesangial cells. Moreover, the inhibition of TGF-β1/Smad3 pathway might be responsible for these changes.

Conclusion: Wogonin may ameliorate renal inflammation and fibrosis in diabetic nephropathy by inhibiting the NF-κB and TGF-β1/Smad3 signaling pathways.

Keywords: diabetic nephropathy; fibrosis; inflammation; wogonin.

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Conflict of interest statement

The authors declare that they have no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Molecular structure of wogonin.
Figure 2
Figure 2
Primary metabolic parameters in mice.
Figure 3
Figure 3
Pathology results in the kidney of mice.
Figure 4
Figure 4
Expression of renal inflammatory cytokines and NF-κB signaling pathway in the kidney of mice.
Figure 5
Figure 5
Immunohistochemistry and Western blot results of ECM in the kidney of mice.
Figure 6
Figure 6
Expression of TGF-β1/Smad3 signaling pathway in the kidney of mice.
Figure 7
Figure 7
Cell viability of SV40 treated with different concentrations of wogonin.
Figure 8
Figure 8
Analysis of inflammatory cytokines and NF-κB signaling pathway in SV40.
Figure 9
Figure 9
The expression of ECM and TGF-β1/Smad3 signaling pathway in SV40.
See this image and copyright information in PMC

References

    1. Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: distinct or continuum? Indian J Endocrinol Metab. 2016;20(4):546. doi:10.4103/2230-8210.183480 - DOI - PMC - PubMed
    1. Gheith O, Farouk N, Nampoory N, Halim MA, Al-Otaibi T. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol. 2016;5:49. - PMC - PubMed
    1. Moreno JA, Gomez-Guerrero C, Mas S, et al. Targeting inflammation in diabetic nephropathy: a tale of hope. Expert Opin Investig Drugs. 2018;27:917–930.doi:10.1080/13543784.2018.1538352 - PubMed
    1. Garrido W, Jara C, Torres A, et al. Blockade of the adenosine A3 receptor attenuates caspase 1 activation in renal tubule epithelial cells and decreases interleukins IL-1β and IL-18 in diabetic rats. Int J Mol Sci. 2019;20(18):4531. doi:10.3390/ijms20184531 - DOI - PMC - PubMed
    1. Niewczas MA, Ficociello LH, Johnson AC, et al. Serum concentrations of markers of TNF alpha and Fas-mediated pathways and renal function in nonproteinuric patients with type 1 diabetes. Clin J Am Soc Nephrol. 2009;4(1):62–70. doi:10.2215/CJN.03010608 - DOI - PMC - PubMed

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