Citrus Auraptene Induces Expression of Brain-Derived Neurotrophic Factor in Neuro2a Cells

Abstract

(1) Background: Our published data have indicated that (1) auraptene (AUR), a citrus ingredient, has neuroprotective effects on the mouse brain, owing to its ability to suppress inflammation, such as causing a reduction in hyperactivation of microglia and astrocytes; (2) AUR has the ability to trigger phosphorylation (activation) of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) in neuronal cells; (3) AUR has the ability to induce glial cell line-derived neurotrophic factor (GDNF) synthesis/secretion in rat C6 glioma cells. The well-established fact that the ERK-CREB pathway plays an important role in the production of neurotrophic factors, including GDNF and brain-derived neurotrophic factor (BDNF), prompted us to investigate whether AUR would also have the ability to induce BDNF expression in neuronal cells. (2) Methods: Mouse neuroblastoma neuro2a cells were cultured and the effects of AUR on BDNF mRNA expression and protein content were evaluated by RT-PCR and ELISA, respectively. (3) Results: The levels of BDNF mRNA and secreted BDNF were significantly increased by AUR in a dose- and time-dependent manner in neuro2a cells. (4) Conclusion: The induction of BDNF in neuronal cells might be, in part, one of the mechanisms accounting for the neuroprotective effects of AUR.

Isolation and Characterization of Neuroprotective Components from Citrus Peel and Their Application as Functional Food

“…53) GDNF, which was originally found as a trophic agent for midbrain dopamine neurons, has pronounced neuroprotective effects in various nervous system pathologies, including ischemic brain damage and neurodegenerative diseases. 54) AUR also slightly but significantly induced bdnf gene expression via the upregulated ERK/CREB pathway in neuro2a cells. 55) Those in vitro study results suggested that the induction of neurotrophic factor in astrocytes and neurons may be one of the mechanisms partially accounting for the neuroprotective effects of AUR.…”

“…54) AUR also slightly but significantly induced bdnf gene expression via the upregulated ERK/CREB pathway in neuro2a cells. 55) Those in vitro study results suggested that the induction of neurotrophic factor in astrocytes and neurons may be one of the mechanisms partially accounting for the neuroprotective effects of AUR.…”

Auraptene and umbelliprenin: a review on their latest literature acquisitions

“…The same pattern was observed for the expression of GDNF mRNA. As a continuation of their studies, Furukawa et al (2020) determined also that auraptene had a deep effect on the release and expression of the brain-derived neurotrophic factor (BDNF) in mouse neuroblastoma 2a cells (Furukawa et al 2020).…”

Potency of Selected Berries, Grapes, and Citrus Fruit as Neuroprotective Agents

“…e induction of the brain-derived neurotrophic factor (BDNF) in neuronal cells was suggested to be one of the mechanisms accounting for the neuroprotective effects exerted by AUR. e BDNF mRNA levels and secreted BDNF in neuro-2a cells were significantly increased by AUR in a dose-and time-dependent manner [132].…”

“…7-[(2E)-3,7-Dimethylocta-2,6-dienoxy]chromen-2-one (auraptene) is a coumarin derivative, which has been reported to possess various pharmacological properties including neuroprotective effects [131] on the mouse brain by suppressing inflammation, e.g., through reduction in hyperactivation of microglia and astrocytes [132]. e antiinflammatory effects were not only on the peripheral organs but also the brain of a mouse model of global cerebral ischemia [133,134] and lipopolysaccharide-(LPS-) induced systemic inflammation [135,136].…”