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. 2021 Nov 1;13(11):3921.
doi: 10.3390/nu13113921.

Protective Effects of Nootkatone on Renal Inflammation, Apoptosis, and Fibrosis in a Unilateral Ureteral Obstructive Mouse Model

Affiliations

Protective Effects of Nootkatone on Renal Inflammation, Apoptosis, and Fibrosis in a Unilateral Ureteral Obstructive Mouse Model

Chang-Mu Chen et al. Nutrients. .

Abstract

Nootkatone is one of the major active ingredients of Alpiniae oxyphyllae, which has been used as both food and medicinal plants for the treatment of diarrhea, ulceration, and enuresis. In this study, we aimed to investigate whether nootkatone treatment ameliorated the progression of chronic kidney diseases (CKD) and clarified its underlying mechanisms in an obstructive nephropathy (unilateral ureteral obstructive; UUO) mouse model. Our results revealed that nootkatone treatment preventively decreased the pathological changes and significantly mitigated the collagen deposition as well as the protein expression of fibrotic markers. Nootkatone could also alleviate oxidative stress-induced injury, inflammatory cell infiltration, and renal cell apoptotic death in the kidneys of UUO mice. These results demonstrated for the first time that nootkatone protected against the progression of CKD in a UUO mouse model. It may serve as a potential therapeutic candidate for CKD intervention.

Keywords: apoptosis; chronic kidney disease; inflammation; nootkatone; renal fibrosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of Nootkatone treatment on the renal pathological changes in a UUO mouse model. Vehicle, Nootkatone (NKT), or candesartan (Can; positive control) was orally given to the sham or UUO mice for 14 days. (A) The pathological changes were determined by hematoxylin and eosin (H&E) staining. The kidney injury features, including kidney tubular dilation (yellow arrow), interstitial infiltration (blue arrow), and glomerular tuft adhesion and sclerosis (white arrow) were indicated. Scale bar: 50 μm. (B) The histopathological scoring is shown Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group.
Figure 2
Figure 2
Effects of Nootkatone treatment on the collagen deposition in the kidneys of UUO mice. Vehicle, Nootkatone (NKT), or candesartan (Can; positive control) was orally given to the sham or UUO mice for 14 days. Collagen deposition was determined by Masson’s Trichrome staining (A). a, Control; b, UUO; c, NTK; d, UUO+NTK; e, Can; f, UUO+Can. Scale bar: 50 μm. The quantification is shown in (B). Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group.
Figure 3
Figure 3
Effects of Nootkatone treatment on the renal pathological changes and collagen deposition in a UUO mouse model. Vehicle or Nootkatone (NKT) was orally given to the sham or UUO mice for 28 days. The pathological changes determined by H&E staining (A). The collagen deposition was determined by Masson’s trichrome staining (B). Scale bar: 50 μm. Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group.
Figure 4
Figure 4
Effects of Nootkatone treatment on the renal fibrosis in the UUO kidneys. Vehicle or Nootkatone (NKT) was orally given to the sham or UUO mice for 14 days. Protein expression levels of the fibrotic signaling markers were determined by Western blotting (A). The quantification is shown in (B). Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group.
Figure 5
Figure 5
Effects of Nootkatone treatment on oxidative stress injury in the UUO kidneys. Vehicle or Nootkatone (NKT) was orally given to the sham or UUO mice for 14 days. Protein expression levels of the oxidative stress markers were determined by Western blotting (A). The quantification is shown in (B). Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group.
Figure 6
Figure 6
Effects of Nootkatone on the inflammatory cell infiltration in the UUO kidneys. Vehicle or Nootkatone (NKT) was orally given to the sham or UUO mice for 14 days. Protein expression levels of pro-inflammatory signaling molecules were determined by Western blotting (A). The changes in the protein expression of both neutrophil marker Ly6G and macrophage marker F4/80 by IHC are shown in (B,C), respectively. a, Control; b, UUO; c, NTK; d, UUO+NTK. Scale bar: 50 μm. Data are presented as mean ± SD (n = 6). * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group. α-T: α-Tubulin.
Figure 7
Figure 7
Effects of Nootkatone treatment on the renal cell apoptosis in the kidneys of UUO mice. Vehicle or Nootkatone (NKT) was orally given to the sham or UUO mice for 14 days. Protein expression levels of apoptotic molecules were determined by Western blotting (A). The TUNEL-positive cells are shown in (B). Data are presented as mean ± SD (n = 6). a, Control; b, UUO; c, NTK; d, UUO+NTK. * p < 0.05 vs. the sham control group. # p < 0.05 vs. the UUO group. C-C3: Cleaved Caspase-3; C-PARP1: Cleaved PARP1. (C) A schematic summary of our main findings for the effects of NKT on the progression of chronic CKD in a UUO mouse model.

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References

    1. Carney E.F. The impact of chronic kidney disease on global health. Nat. Rev. Nephrol. 2020;16:251. doi: 10.1038/s41581-020-0268-7. - DOI - PubMed
    1. Nogueira A., Pires M.J., Oliveira P.A. Pathophysiological mechanisms of renal fibrosis: A review of animal models and therapeutic strategies. In Vivo. 2017;31:1–22. doi: 10.21873/invivo.11019. - DOI - PMC - PubMed
    1. Grande M.T., Lopez-Novoa J.M. Fibroblast activation and myofibroblast generation in obstructive nephropathy. Nat. Rev. Nephrol. 2009;5:319–328. doi: 10.1038/nrneph.2009.74. - DOI - PubMed
    1. Sean Eardley K., Cockwell P. Macrophages and progressive tubulointerstitial disease. Kidney Int. 2005;68:437–455. doi: 10.1111/j.1523-1755.2005.00422.x. - DOI - PubMed
    1. Tammaro A., Stroo I., Rampanelli E., Blank F., Butter L.M., Claessen N., Takai T., Colonna M., Leemans J.C., Florquin S., et al. Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy. PLoS ONE. 2013;8:e82498. doi: 10.1371/journal.pone.0082498. - DOI - PMC - PubMed