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Andrographolide prevents renal fibrosis via decelerating lipotoxicity-mediated premature senescence of tubular epithelial cells

  • 0Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, School of Medical Technology, Guangdong Medical University, Dongguan 523808, China.
Biochemical Pharmacology +

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November 11, 2024

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November 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Andrographolide (AP) reduces kidney fibrosis by decreasing lipid accumulation and oxidative stress in mice on a high-fat diet. AP activates AMP-activated protein kinase (AMPK), preventing kidney cell damage and fibrosis progression.

Area Of Science

  • Nephrology
  • Pharmacology
  • Cell Biology

Background

  • Excessive lipid accumulation in early chronic kidney disease (CKD) promotes oxidative stress, mitochondrial damage, and kidney fibrosis.
  • Andrographolide (AP), a natural compound, shows potential in metabolic disorders.

Purpose Of The Study

  • To investigate the therapeutic effects of Andrographolide (AP) on high-fat diet (HFD)-induced kidney injury and fibrosis.
  • To elucidate the underlying mechanisms of AP's protective action, focusing on lipid metabolism, oxidative stress, and cellular senescence.

Main Methods

  • Mice were fed a high-fat diet (HFD) to induce kidney injury and fibrosis.
  • AP treatment was administered to assess its effects on renal lipid accumulation, oxidative stress, mitochondrial function, and tubular cell senescence.
  • The study examined the impact of AP on senescence-associated secretory phenotype (SASP) and fibroblast activation.
  • AP's role as an AMP-activated protein kinase (AMPK) activator was investigated.

Main Results

  • AP treatment counteracted HFD-induced tubule injury and interstitial fibrosis in mice.
  • AP decreased renal lipid accumulation, attenuated lipotoxicity-mediated oxidative stress, and improved mitochondrial dysfunction.
  • AP significantly reduced tubular cell senescence and inhibited SASP secretion.
  • AP suppressed fibroblast proliferation and activation, suggesting a paracrine inhibitory effect.
  • AP was identified as an AMPK activator, ameliorating renal lipid accumulation and protecting against tubular cell senescence and fibroblast activation.

Conclusions

  • Andrographolide (AP) effectively protects against high-fat diet-induced kidney injury and fibrosis.
  • AP ameliorates renal damage by reducing lipotoxicity, oxidative stress, and premature tubular cell senescence via AMPK activation.
  • Targeting lipotoxicity-mediated senescence in tubular cells presents a promising therapeutic strategy for CKD prevention and treatment using AP.

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