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Biochanin A alleviates unilateral ureteral obstruction-induced renal interstitial fibrosis and inflammation by inhibiting the TGF-β1/Smad2/3 and NF-kB/NLRP3 signaling axis in mice.
- Source :
-
Life Sciences . Jun2022, Vol. 298, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- Tubulointerstitial fibrosis, a frequent complication of chronic kidney disease (CKD) is a major public health issue. Biochanin A (BCA), an isoflavone, has numerous pharmacological activities. However, its effect on renal fibrosis and underlying molecular mechanism has not yet been clarified. This study explored the effect of BCA on renal tubulointerstitial fibrosis and inflammation in mice. The mouse model of unilateral ureteral obstruction (UUO) in vivo and transforming growth factor (TGF)-β1 activated renal fibroblast (NRK 49F) cells in vitro model were used to assess the antifibrotic effect of BCA. Biochemical analysis, histopathology, western blotting, and immunofluorescent staining methods were performed to elucidate the mechanism of BCA. In vitro, BCA suppressed the expression of fibrogenic proteins in TGF-β1-activated renal fibroblasts. The treatment with BCA displayed less tubular injury, prevented the aberrant accumulation of extracellular matrix (ECM) components, and inhibited the TGF-β1/Smad2/3 signaling axis in the kidneys. Furthermore, BCA impeded the phosphorylation of NF-kB(p65) and blunted the expression of inflammatory genes in the obstructed kidneys. The UUO induced expressions of nod-like receptor protein 3 (NLRP3), active caspase 1, interleukin(IL)-18, and IL-1β proteins were decreased in the BCA treated groups. We also found the increased expression of redox-sensitive nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins in BCA treated groups compared to the UUO control. These findings indicate that BCA has a therapeutic benefit against renal fibrosis, and the ameliorative effect is mediated via inhibiting the TGF-β1/Smad2/3 and NF-kB/NLRP3 signaling axis. [Display omitted] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 298
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 156288154
- Full Text :
- https://doi.org/10.1016/j.lfs.2022.120527