# Metabolic Reprogramming by Andrographolide: Enhanced Pentose Phosphate Pathway and Antioxidant Capacity in Cortical Astrocytes

## TL;DR

This study shows that andrographolide boosts antioxidant capacity and alters glucose metabolism in brain astrocytes, potentially offering neuroprotection.

## Contribution

The study reveals andrographolide's novel effect on astrocytic metabolic reprogramming via the pentose phosphate pathway and Wnt signaling.

## Key findings

- Andrographolide increases glucose uptake and antioxidant capacity in astrocytes.
- It enhances glucose-6-phosphate dehydrogenase activity and NADPH availability.
- The compound promotes redox maintenance over energy production in astrocytes.

## Abstract

Background/Objectives: Astrocytes are key regulators of brain energy homeostasis, integrating glucose metabolism with antioxidant support for neuronal function. Dysregulation of these processes contributes to neurodegenerative diseases, including Alzheimer’s disease. Andrographolide, a bioactive diterpenoid from Andrographis paniculata, has been reported to exert neuroprotective effects through the modulation of Wnt/β–catenin signaling and neuronal metabolism; however, its actions on astrocytic metabolic pathways remain insufficiently characterized. Methods: Here, we investigated the effects of andrographolide on metabolic and redox parameters in primary mouse cortical astrocytes. Results: Andrographolide increased glucose uptake and antioxidant capacity without affecting AMPK activation or the activity of core glycolytic enzymes. Instead, it selectively enhanced glucose-6-phosphate dehydrogenase activity, promoting glucose flux through the pentose phosphate pathway in a partially Wnt-dependent manner. This metabolic reprogramming was associated with increased NADPH availability and glutathione levels, together with a reduced ATP/ADP ratio, consistent with a shift toward redox maintenance rather than maximal energy production. Conclusions: Collectively, these findings highlight astrocytic metabolic plasticity as a relevant and underexplored target of andrographolide and support the concept that natural compounds can enhance brain resilience by modulating glial redox metabolism.