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.
Highlights
Auraptene (7-geranyloxycoumarin; AUR), a citrus coumarin derivative, has been revealed to possess valuable pharmacological properties, including anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-helicobacter, anti-diabetic, anti-hypertensive [1], and neuroprotective ones [2].We previously demonstrated that AUR exerts anti-inflammatory effects in peripheral organs and the brain, as found from studies using a mouse model of global cerebral ischemia [3,4] and lipopolysaccharide (LPS)-induced systemic inflammation [5,6]
We revealed that AUR acted as an inducer of brain-derived neurotrophic factor (BDNF) in neuro2a cells
The present findings suggested that some of the neuroprotective effects exerted by AUR could, in part, have resulted from enhanced synthesis/secretion of BDNF by neurons themselves
Summary
Auraptene (7-geranyloxycoumarin; AUR), a citrus coumarin derivative, has been revealed to possess valuable pharmacological properties, including anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-helicobacter, anti-diabetic, anti-hypertensive [1], and neuroprotective ones [2]. We previously demonstrated that AUR exerts anti-inflammatory effects in peripheral organs and the brain, as found from studies using a mouse model of global cerebral ischemia [3,4] and lipopolysaccharide (LPS)-induced systemic inflammation [5,6]. Molecules 2020, 25, 1117 such as glial cell line-derived neurotrophic factor (GDNF) [10] and brain-derived neurotrophic factor (BDNF) [11,12]. Our latest study revealed that AUR has the ability to induce GDNF expression in C6 cells by triggering the protein kinase A (PKA)/ERK/CREB pathway [9]. Using neuro2a cells, an immortalized cell line of murine nerve cells, we examined whether AUR would have the ability to induce BDNF expression in these cells
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