Abstract
Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-β1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24 h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-β1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-β1 reduction.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- α-SMA:
-
α-Smooth muscle actin
- BC:
-
Betweenness centrality
- BCL-2:
-
B-cell lymphoma-2
- BUN:
-
Blood urea nitrogen
- CASP3:
-
Caspase-3
- CKD:
-
Chronic kidney disease
- DC:
-
Degree centrality
- ECM:
-
Extracellular matrix
- ELISA:
-
Enzyme-linked immunosorbent assay
- EPO:
-
Erythropoietin
- EPOR:
-
Erythropoietin receptor
- ESKD:
-
End-stage renal disease
- FN:
-
Fibronectin
- COL I:
-
Collagen I
- HE:
-
Hematoxylin and eosin
- HIF :
-
Hypoxia-inducible factor
- HIF -1a:
-
Hypoxia-inducible factor-1a
- HIF -2a:
-
Hypoxia-inducible factor-2a
- MDM2 :
-
Murine double minute2
- PARP1:
-
Poly(ADP-ribose) polymerase 1
- PLT:
-
Platelet count
- Scr:
-
Serum creatinine
- TGF-β1:
-
Transforming growth factor-β1
- UP:
-
Urine protein
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This work was supported by the Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine (Grant No. QJRC2022031).
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The authors declare that all data were generated in-house and that no paper mill was used. X.Z.: conception/design of the work, methodology, validation, formal analysis, investigation, data curation, visualization, writing and editing. X.M.: methodology, validation, editing. D.L.: investigation, acquisition of data. B.L.: curation, supervision. Yixin Rui: acquisition of data. H.X.: acquisition of data. R.L.: conception/design of the work, writing—review and editing, supervision, project administration, funding acquisition. N.Z.: conceptualization, writing—review and editing, supervision, project administration.
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Zhang, XM., Min, XR., Li, D. et al. The protective effect and mechanism of piperazine ferulate in rats with 5/6 nephrectomy-caused chronic kidney disease. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02976-1
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DOI: https://doi.org/10.1007/s00210-024-02976-1