Open Access

Astragaloside IV ameliorates diabetic nephropathy in db/db mice by inhibiting NLRP3 inflammasome‑mediated inflammation

  • Authors:
    • Hui Feng
    • Xiaoyun Zhu
    • Yang Tang
    • Shouqiang Fu
    • Bingtan Kong
    • Ximing Liu
  • View Affiliations

  • Published online on: July 5, 2021     https://doi.org/10.3892/ijmm.2021.4996
  • Article Number: 164
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic nephropathy (DN) is a primary cause of end‑stage renal disease. Despite the beneficial effects of astragaloside IV (AS)‑IV on renal disease, the underlying mechanism of its protective effects against DN has not been fully determined. The aims of the present study were to assess the effects of AS‑IV against DN in db/db mice and to explore the mechanism of AS‑IV involving the NLR family pyrin domain containing 3 (NLRP3), caspase‑1 and interleukin (IL)‑1β pathways. The 8‑week‑old db/db mice received 40 mg/kg AS‑IV once a day for 12 weeks via intragastric administration. Cultured mouse podocytes were used to further confirm the underlying mechanism in vitro. AS‑IV effectively reduced weight gain, hyperglycemia and the serum triacylglycerol concentration in db/db mice. AS‑IV also reduced urinary albumin excretion, urinary albumin‑to‑creatinine ratio and creatinine clearance rate, as well as improved renal structural changes, accompanied by the upregulation of the podocyte markers podocin and synaptopodin. AS‑IV significantly inhibited the expression levels of NLRP3, caspase‑1 and IL‑1β in the renal cortex, and reduced the serum levels of tumor necrosis factor (TNF)‑α and monocyte chemoattractant protein‑1. In high glucose‑induced podocytes, AS‑IV significantly improved the expression levels of NLRP3, pro‑caspase‑1 and caspase‑1, and inhibited the cell viability decrease in a dose‑dependent manner, while NLRP3 overexpression eliminated the effect of AS‑IV on podocyte injury and the inhibition of the NLRP3 and caspase‑1 pathways. The data obtained from in vivo and in vitro experiments demonstrated that AS‑IV ameliorated renal functions and podocyte injury and delayed the development of DN in db/db mice via anti‑NLRP3 inflammasome‑mediated inflammation.
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August-2021
Volume 48 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Feng H, Zhu X, Tang Y, Fu S, Kong B and Liu X: Astragaloside IV ameliorates diabetic nephropathy in <em>db/db</em> mice by inhibiting NLRP3 inflammasome‑mediated inflammation. Int J Mol Med 48: 164, 2021.
APA
Feng, H., Zhu, X., Tang, Y., Fu, S., Kong, B., & Liu, X. (2021). Astragaloside IV ameliorates diabetic nephropathy in <em>db/db</em> mice by inhibiting NLRP3 inflammasome‑mediated inflammation. International Journal of Molecular Medicine, 48, 164. https://doi.org/10.3892/ijmm.2021.4996
MLA
Feng, H., Zhu, X., Tang, Y., Fu, S., Kong, B., Liu, X."Astragaloside IV ameliorates diabetic nephropathy in <em>db/db</em> mice by inhibiting NLRP3 inflammasome‑mediated inflammation". International Journal of Molecular Medicine 48.2 (2021): 164.
Chicago
Feng, H., Zhu, X., Tang, Y., Fu, S., Kong, B., Liu, X."Astragaloside IV ameliorates diabetic nephropathy in <em>db/db</em> mice by inhibiting NLRP3 inflammasome‑mediated inflammation". International Journal of Molecular Medicine 48, no. 2 (2021): 164. https://doi.org/10.3892/ijmm.2021.4996