Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

Neural Plasticity
Lorena Varela-NallarNibaldo C Inestrosa

Abstract

Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that...Continue Reading

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Citations

Aug 10, 2016·Neurobiology of Aging·Daniela S RiveraNibaldo C Inestrosa
Sep 7, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Clara Herrera-ArozamenaMaría Isabel Rodríguez-Franco
Sep 15, 2016·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Rivka Noelanders, Kris Vleminckx
Apr 18, 2018·Journal of Alzheimer's Disease : JAD·Juan M ZolezziNibaldo C Inestrosa
Nov 9, 2019·Molecular Neurobiology·Carolina B LindsayNibaldo C Inestrosa
Jun 11, 2019·The International Journal of Neuropsychopharmacology·Jing-Jing ZhangBo Jiang
Oct 13, 2020·Frontiers in Cell and Developmental Biology·Sebastian B ArredondoLorena Varela-Nallar
Feb 9, 2021·Mechanisms of Ageing and Development·Hang LiuYing Ma
Jun 1, 2021·Journal of Psychiatric Research·Luiz K S KanazawaRoberto Andreatini

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Methods Mentioned

BETA
Protein Assay
confocal microscopy
transgenic
transgenics

Software Mentioned

GraphPad
ImageJ
Prism

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