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Andrographolide enhances astrocyte antioxidant capacity by shifting glucose metabolism through the pentose phosphate pathway. This natural compound supports brain resilience by modulating glial redox balance, offering potential for neurodegenerative disease intervention.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Astrocytes regulate brain energy and antioxidant defenses, crucial for neuronal function.
  • Metabolic dysregulation in astrocytes is implicated in neurodegenerative diseases like Alzheimer's.
  • Andrographolide shows neuroprotection but its effects on astrocyte metabolism are unclear.

Purpose of the Study:

  • To investigate andrographolide's impact on metabolic and redox parameters in primary mouse cortical astrocytes.
  • To elucidate the specific metabolic pathways modulated by andrographolide in astrocytes.

Main Methods:

  • Primary mouse cortical astrocytes were treated with andrographolide.
  • Glucose uptake, antioxidant capacity, enzyme activities, and cellular energy status were measured.
  • Wnt/β-catenin signaling pathway involvement was assessed.

Main Results:

  • Andrographolide increased glucose uptake and antioxidant capacity.
  • It selectively enhanced glucose-6-phosphate dehydrogenase, promoting pentose phosphate pathway flux.
  • This occurred via Wnt/β-catenin signaling, increasing NADPH and glutathione, and reducing ATP/ADP ratio.

Conclusions:

  • Andrographolide reprograms astrocytic metabolism towards redox maintenance.
  • Astrocytic metabolic plasticity is a key target for andrographolide's neuroprotective effects.
  • Natural compounds can bolster brain resilience by modulating glial redox metabolism.