Andrographolide stimulates neurogenesis in the adult hippocampus

This may be in mice but hell it should be added to the stroke strategy and research sponsored to find out if this works in humans. Damn, so much research to do and no one to direct it.
http://scholar.google.com/scholar_url?url=http://downloads.hindawi.com/journals/np/aip/935403.pdf&hl=en&sa=X&scisig=AAGBfm3ZwPw89YwMS9BnvOh-BMJyfx92HA&nossl=1&oi=scholaralrt

Lorena Varela-Nallar, PhD 1*, Sebastian B. Arredondo, MSc1, Cheril Tapia-Rojas, MSc 2,

Juan Hancke, DVM 3, and Nibaldo C. Inestrosa, PhD 2,4,5,*.

1Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad

de Medicina, Universidad Andrés Bello, Santiago, Chile

2Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y

Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile,

Santiago, Chile.

4Instituto de Farmacología y Morfofisiología, Universidad Austral de Chile, Valdivia,

Chile.

5Center for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of

New South Wales, Sydney, Australia

6Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de

Magallanes, Punta Arenas, Chile.

Running title: Andrographolide stimulates adult neurogenesis

*Correspondence: Dr. Lorena Varela-Nallar, Center for Biomedical Research, Universidad

Andrés Bello, República 239, 8370146, Santiago, Chile. E-mail: lorena.varela@unab.cl;

Dr. Nibaldo C. Inestrosa, CARE Biomedical Center, Pontificia Universidad Católica de

Chile, Alameda 340, P. O. Box 114-D, Santiago, Chile. E-mail: ninestrosa@bio.puc.cl.

2

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-3â (GSK-3â), a key

enzyme of the Wnt/â-catenin signaling cascade. Since this signaling pathway regulates

neurogenesis in the adult hippocampal dentate gyrus, we evaluated whether ANDRO is

able to stimulate this process. Treatment with ANDRO increased neural progenitor cell

proliferation and the number of immature neurons in the hippocampus of 2- and 10-monthold

mice compared to age-matched control mice. Moreover, ANDRO stimulated a net

increase in neurogenesis increasing the number of newborn dentate granule neurons. Also,

the effect of ANDRO was evaluated in the double transgenic APPswe/PS1ÄE9 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/PS1ÄE9 mice determined by increased levels of â-

catenin, the inactive form of GSK-3â, and NeuroD1, a Wnt target gene involved in

neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult

hippocampus suggesting that this drug could be used as a therapy in diseases in which

neurogenesis is affected.