Protection by [6]-shogaol against lipopolysaccharide-induced toxicity in murine astrocytes is related to production of brain-derived neurotrophic factor

► Primary cortical astrocytes were cultured from neonatal rats. ► [6]-Shogaol provided protection of astrocytes from the cytotoxicity induced by LPS. ► [6]-Shogaol showed anti-oxidant activity and BDNF increases in LPS-treated cultured astrocytes. ► The protective effects of [6]-shogaol are associated with increased BDNF and CREB phosphorylation. [6]-Shogaol has beneficial effects in spinal neuronal regeneration, but associated molecules and mechanisms are not identified. Neurotrophic factors, including brain-derived neurotrophic factor (BDNF), are associated with proliferation and differentiation of neuronal cells and exert a neuroprotective effect in neurodegenerative models. We investigated whether treatment with [6]-shogaol increases BDNF expression in lipopolysaccharide (LPS)-treated astrocytes, and examined the effect of [6]-shogaol on neuronal protection. [6]-Shogaol significantly attenuated the cell death induced by LPS. Western blotting showed that [6]-shogaol treatment reduced Bax expression and increased B-cell lymphoma (Bcl)-2 and BclxL expression in LPS-treated cells, consistent with the effects of BDNF treatment. Furthermore, K252a, a blocker of neurotrophic factors, attenuated the cellular protective effects of [6]-shogaol and BDNF. This study provides the first evidence that [6]-shogaol increases the expression of BDNF in LPS-treated astrocytes. Furthermore, these experimental results indicate that production of BDNF in astrocytes might be related to altered cell viability following [6]-shogaol treatment. Thus, the neuroprotective effects of [6]-shogaol is mediated by up-regulation of BDNF.