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Updated: Jan 8, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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Lycopene inhibits ER stress and apoptosis while modulating PI3K/AKT and enhancing antioxidant and anti-apoptotic

Lijun Zheng1, Hui Zhang2, Yuchao Sun3

  • 1Nursing Department, The Fourth Affiliated Hospital of School of Medicine, Zhejiang University, Yiwu, China.

Plos One
|December 23, 2025
PubMed

Insights

Lycopene, a potent antioxidant, shows promise in protecting against acute kidney injury (AKI). It reduces kidney damage and cell death by targeting oxidative stress and apoptosis through the PI3K/Akt pathway.

Area of Science:

  • Nephrology
  • Biochemistry
  • Pharmacology

Background:

  • Acute kidney injury (AKI) presents significant clinical challenges with limited treatment options.
  • Oxidative stress and apoptosis are key pathological mechanisms in AKI development.
  • Lycopene, a natural antioxidant, has potential therapeutic applications.

Purpose of the Study:

  • To investigate the renoprotective effects of lycopene in experimental models of AKI.
  • To elucidate the molecular mechanisms underlying lycopene's protective actions, focusing on the PI3K/Akt pathway.
  • To evaluate lycopene's efficacy in both in vivo and in vitro AKI models.

Main Methods:

  • Murine model of sepsis-induced AKI using cecal ligation and puncture (CLP).
  • In vitro cellular AKI models induced by lipopolysaccharide (LPS) and hydrogen peroxide (H₂O₂).
  • Assessment of renal histopathology, serum biomarkers, oxidative stress markers, apoptosis markers, and Western blotting for key proteins.
  • PI3K manipulation using siRNA and cDNA transfection to confirm pathway dependency.

Main Results:

  • Lycopene pretreatment dose-dependently ameliorated renal damage and restored serum biomarkers in CLP-induced AKI.
  • Lycopene suppressed oxidative stress and apoptosis by downregulating p-PI3K, p-Akt, Bax, and Cleaved Caspase-3, while upregulating Nrf 2 and SOD1.
  • Consistent renoprotective effects were observed in LPS- and H₂O₂-induced cellular AKI models.
  • PI3K pathway was confirmed to be essential for lycopene's antioxidant and anti-apoptotic effects.

Conclusions:

  • Lycopene exhibits significant renoprotective effects in AKI models.
  • The protective mechanism involves the PI3K/Akt pathway, leading to reduced oxidative stress and apoptosis.
  • Lycopene activates Nrf 2, counteracting renal damage and supporting its potential as a therapeutic agent for AKI.

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