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Anemonin inhibits sepsis-induced acute kidney injury via mitigating inflammation and oxidative stress

Dan Liu1, Li Li1, Zengyan Li1

  • 1Department of Nephrology, First Affiliated Hospital of Baotou Medical College, Baotou, China.

Biotechnology and Applied Biochemistry
|August 17, 2023
PubMed

Insights

Anemonin (ANE) protects against sepsis-induced acute kidney injury (AKI) by reducing inflammation, oxidative stress, and cell death. This natural compound activates the AMPK/Sirt-1 pathway, offering a potential therapeutic strategy for AKI.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Nephrology

Background:

  • Sepsis-induced acute kidney injury (AKI) is characterized by significant inflammation and oxidative stress (OS).
  • Current treatments for sepsis-induced AKI are limited, highlighting the need for novel therapeutic agents.
  • Natural compounds offer potential avenues for developing new AKI treatments.

Purpose of the Study:

  • To investigate the protective effects of the natural compound Anemonin (ANE) against sepsis-induced AKI.
  • To elucidate the underlying molecular mechanisms of ANE's action, particularly the involvement of the AMPK/Sirt-1 pathway.
  • To evaluate ANE's efficacy in both in vitro and in vivo models of sepsis-induced AKI.

Main Methods:

  • In vitro AKI models were established using renal tubular epithelial cells treated with lipopolysaccharide (LPS).
  • In vivo sepsis-induced AKI models were created in C57BL/6J mice via cecal ligation and puncture (CLP).
  • Cell viability, apoptosis, OS markers, inflammatory cytokines, and key protein expressions (p53, Bax, Bcl2, Caspase3/8/9, AMPK, Sirt-1, FOXO3) were assessed using Western Blot, RT-PCR, and biochemical assays. Kidney pathology was evaluated via H&E staining and immunohistochemistry.

Main Results:

  • Anemonin (ANE) demonstrated dose-dependent protection against LPS-induced apoptosis, inflammation, and OS in renal tubular epithelial cells.
  • ANE treatment activated the AMP-activated protein kinase (AMPK)/Sirt-1 pathway, as evidenced by increased protein levels and confirmed by inhibitor studies (Compound C, EX-527).
  • In vivo, ANE significantly reduced serum creatinine and urea nitrogen levels, mitigated kidney tissue injury, and attenuated OS, inflammation, and apoptosis in CLP-induced septic mice.

Conclusions:

  • Anemonin (ANE) exhibits significant protective effects against sepsis-induced acute kidney injury (AKI).
  • ANE exerts its renoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis.
  • The activation of the AMPK/Sirt-1 pathway is a key mechanism underlying ANE's therapeutic benefits in sepsis-induced AKI.
Keywords:
AMPKacute renal injuryanemonininflammationoxidative stresspathway

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