Punicalagin Activates AMPK/PGC-1α/Nrf2 Cascade in Mice: The Potential Protective Effect against Prenatal Stress

Ke Cao1, Weiqiang Lv1, Shaoqin Hu1

  • 1Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.

Insights

Prenatal stress impairs offspring learning and memory by reducing AMP-activated protein kinase (AMPK) activity. Pomegranate extract (Punicalagin) may counteract these effects, offering a potential maternal nutritional intervention.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Biochemistry

Background:

  • Prenatal stress is linked to adverse offspring health outcomes.
  • Mechanisms and interventions for prenatal stress effects are not well-established.

Purpose of the Study:

  • To investigate the impact of prenatal restraint stress (PRS) on offspring health.
  • To explore the role of AMP-activated protein kinase (AMPK) in PRS-induced deficits.
  • To evaluate Punicalagin (PU) as a potential intervention.

Main Methods:

  • Rat offspring exposed to PRS were assessed for spatial learning and memory.
  • AMPK activity, mitochondrial biogenesis, and antioxidant pathways were analyzed in hippocampus and other tissues.
  • In vitro studies used HT22 and primary hippocampal neurons to assess PU effects on AMPK and cell viability.
  • In vivo studies administered PU to mice.

Main Results:

  • Prenatal stress led to impaired spatial learning and memory in offspring.
  • PRS reduced AMPK activity and mitochondrial/antioxidant pathway proteins in the hippocampus and systemically.
  • Increased maternal glucocorticoids may contribute to systemic AMPK deficiency.
  • Punicalagin activated AMPK, induced mitochondrial biogenesis, and protected neurons from glutamate toxicity.
  • PU administration activated AMPK in mice.

Conclusions:

  • Systemic AMPK deficiency is a key factor in poor outcomes associated with prenatal stress.
  • Punicalagin shows potential as an effective maternal nutritional intervention to mitigate PRS effects.
Abstract