2. Academic Validation
  3. Alpha-cyperone ameliorates renal fibrosis and inflammation in mice with chronic kidney disease via NF-κB and Akt/Nrf2/HO-1 pathways

Alpha-cyperone ameliorates renal fibrosis and inflammation in mice with chronic kidney disease via NF-κB and Akt/Nrf2/HO-1 pathways

  • Immunopharmacol Immunotoxicol. 2025 May 25:1-11. doi: 10.1080/08923973.2025.2507129.
Wei Chen 1,  Jiansong Mao 2,  Chun Li 3,  Jinlian Ke 3
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi, China.
  • 2 Department of Teaching Administration, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China.
  • 3 Department of Nephrology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, China.
PMID: 40415449 DOI: 10.1080/08923973.2025.2507129
Abstract

Background: Renal fibrosis is a hallmark feature of chronic kidney disease (CKD) and contributes to local inflammation and impaired renal function. The study aimed to investigate the effects of an active compound, alpha-cyperone, on renal fibrosis, inflammation, and oxidative stress in CKD mice.

Methods: After subtotal nephrectomy, mice were administered with alpha-cyperone (5, 10, and 20 mg/kg) or captopril (the positive control) daily via oral gavage. Masson trichrome staining and periodic Acid-Schiff staining were performed to measure fibrotic areas and renal histopathological changes. An enzyme-linked immunosorbent assay was conducted to measure inflammatory cytokine levels in mouse serum samples. Superoxide anion concentrations, Reactive Oxygen Species (ROS) level, and superoxide dismutase (SOD) activity were analyzed. Immunohistochemistry was performed to detect inflammatory and oxidative stress markers (Ly6G and 8-OHdG) in mouse renal tissues. Protein levels of factors involved in NF-κB signaling and Akt/Nrf2/HO-1 signaling were quantified by western blotting.

Results: Alpha-cyperone at the dose of 10 mg/kg significantly improved renal functions in CKD model mice and alleviated tubulointerstitial fibrosis, with effects comparable to those of captopril. After CKD modeling, serum levels of inflammatory mediators, Ly6G levels, superoxide anion activity, ROS levels, and 8-OHdG levels were markedly increased, while the activity of antioxidant enzyme SOD was reduced. All these changes were ameliorated by alpha-cyperone or captopril treatment. Moreover, alpha-cyperone inhibited the NF-κB signaling and activated the Akt/Nrf2/HO-1 signaling in renal tissues of CKD mice.

Conclusion: Alpha-cyperone ameliorates renal fibrosis in CKD mice by inhibiting inflammation and oxidative stress via NF-κB and Akt/Nrf2/HO-1 pathways.

Keywords

Alpha-cyperone; chronic kidney disease; inflammation; nephrectomy; oxidative stress.

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