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Pharmaceuticals
Volume 19
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10.3390/ph19010133
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Article

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

by
Pedro Cisternas
1,*,
Paulina Ormazabal
2,
Camila Gherardelli
3,
Marianela Bastías-Pérez
1,4,
Jose Brito-Valenzuela
5 and
Nibaldo C. Inestrosa
3,6,*
1
Núcleo de Investigación en Nutrición y Ciencias Alimentarias (NINCAL), Facultad de Salud y Ciencias Sociales, Universidad de Las Américas, Santiago 7500658, Chile
2
Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Lota 2465, Providencia, Santiago 7510157, Chile
3
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Av. Bernardo O’Higgins 340, Santiago 8331150, Chile
4
Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), E-28029 Madrid, Spain
5
Departamento de Obstetricia y Puericultura, Facultad de Medicina, Universidad de Concepción, Concepción 4030000, Chile
6
Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Escuela de Medicina, Universidad de Magallanes, Punta Arenas 6200000, Chile
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2026, 19(1), 133; https://doi.org/10.3390/ph19010133
Submission received: 13 November 2025 / Revised: 30 December 2025 / Accepted: 9 January 2026 / Published: 12 January 2026
(This article belongs to the Special Issue Metabolism, Inflammation and Neurodegeneration: Natural Compounds as Therapeutic Agents)
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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.
Keywords: astrocytes; andrographolide; glucose metabolism; neuroprotection; Alzheimer disease astrocytes; andrographolide; glucose metabolism; neuroprotection; Alzheimer disease
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MDPI and ACS Style

Cisternas, P.; Ormazabal, P.; Gherardelli, C.; Bastías-Pérez, M.; Brito-Valenzuela, J.; Inestrosa, N.C. Metabolic Reprogramming by Andrographolide: Enhanced Pentose Phosphate Pathway and Antioxidant Capacity in Cortical Astrocytes. Pharmaceuticals 2026, 19, 133. https://doi.org/10.3390/ph19010133

AMA Style

Cisternas P, Ormazabal P, Gherardelli C, Bastías-Pérez M, Brito-Valenzuela J, Inestrosa NC. Metabolic Reprogramming by Andrographolide: Enhanced Pentose Phosphate Pathway and Antioxidant Capacity in Cortical Astrocytes. Pharmaceuticals. 2026; 19(1):133. https://doi.org/10.3390/ph19010133

Chicago/Turabian Style

Cisternas, Pedro, Paulina Ormazabal, Camila Gherardelli, Marianela Bastías-Pérez, Jose Brito-Valenzuela, and Nibaldo C. Inestrosa. 2026. "Metabolic Reprogramming by Andrographolide: Enhanced Pentose Phosphate Pathway and Antioxidant Capacity in Cortical Astrocytes" Pharmaceuticals 19, no. 1: 133. https://doi.org/10.3390/ph19010133

APA Style

Cisternas, P., Ormazabal, P., Gherardelli, C., Bastías-Pérez, M., Brito-Valenzuela, J., & Inestrosa, N. C. (2026). Metabolic Reprogramming by Andrographolide: Enhanced Pentose Phosphate Pathway and Antioxidant Capacity in Cortical Astrocytes. Pharmaceuticals, 19(1), 133. https://doi.org/10.3390/ph19010133

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