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Forschungsdatenbank PMU-SQQUID

Chroman-like cyclic prenylflavonoids promote neuronal differentiation and neurite outgrowth and are neuroprotective.
Oberbauer, E; Urmann, C; Steffenhagen, C; Bieler, L; Brunner, D; Furtner, T; Humpel, C; Bäumer, B; Bandtlow, C; Couillard-Despres, S; Rivera, FJ; Riepl, H; Aigner, L;
J Nutr Biochem. 2013; 24(11):1953-1962
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Bieler Lara Sophie
Couillard-Després Sébastien
Furtner Tanja
Oberbauer Eleni
Rivera Gomez-Barris Francisco J.

Abstract

Flavonoids target a variety of pathophysiological mechanisms and are therefore increasingly considered as compounds encompassed with therapeutic potentials in diseases such as cancer, diabetes, arteriosclerosis, and neurodegenerative diseases and mood disorders. Hops (Humulus lupulus L.) is rich in flavonoids such as the flavanone 8-prenylnaringenin, which is the most potent phytoestrogen identified so far, and the prenylchalcone xanthohumol, which has potent tumor-preventive, anti-inflammatory and antiviral activities. In the present study, we questioned whether hops-derived prenylflavonoids and synthetic derivatives thereof act on neuronal precursor cells and neuronal cell lines to induce neuronal differentiation, neurite outgrowth and neuroprotection. Therefore, mouse embryonic forebrain-derived neural precursors and Neuro2a neuroblastoma-derived cells were stimulated with the prenylflavonoids of interest, and their potential to activate the promoter of the neuronal fate-specific doublecortin gene and to stimulate neuronal differentiation and neurite outgrowth was analyzed. In this screening, we identified highly "neuroactive" compounds, which we termed "enhancement of neuronal differentiation factors" (ENDFs). The most potent molecule, ENDF1, was demonstrated to promote neuronal differentiation of neural stem cells and neurite outgrowth of cultured dorsal root ganglion neurons and protected neuronal PC12 cells from cobalt chloride-induced as well as cholinergic neurons of the nucleus basalis of Meynert from deafferentation-induced cell death. The results indicate that hops-derived prenylflavonoids such as ENDFs might be powerful molecules to promote neurogenesis, neuroregeneration and neuroprotection in cases of chronic neurodegenerative diseases, acute brain and spinal cord lesion and age-associated cognitive impairments.


Useful keywords (using NLM MeSH Indexing)

Animals

Cell Death/drug effects

Cell Differentiation/drug effects*

Cell Line

Chick Embryo

Chromans/pharmacology*

Cobalt/toxicity

Flavanones/pharmacology

Flavonoids/pharmacology*

Ganglia, Spinal/cytology

Ganglia, Spinal/drug effects

Mice

Microtubule-Associated Proteins/metabolism

Neural Stem Cells/drug effects*

Neurites/physiology*

Neurogenesis*

Neuropeptides/metabolism

PC12 Cells

Propiophenones/pharmacology

Rats

Tumor Cells, Cultured


Find related publications in this database (Keywords)

Prenylflavonoids
Neurite outgrowth
Neuroprotection
Neural stem cells
Doublecortin
Retinoic acid
NGF
Xanthohumol
Humulus lupulus L