[PMID]: | 28489907 |
[Au] Autor: | Luo L; Kim SW; Lee HK; Kim ID; Lee H; Lee JK |
[Ad] Endereço: | Department of Anatomy, Inha University School of Medicine, Inchon, Korea. |
[Ti] Título: | Anti-oxidative effects of 4-hydroxybenzyl alcohol in astrocytes confer protective effects in autocrine and paracrine manners. |
[So] Source: | PLoS One;12(5):e0177322, 2017. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata Blume (GEB), a traditional herbal medicine used in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in the brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc-toxic effects have been implicated in the postischemic brain. Here, the authors investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to identify the underlying molecular mechanisms involved. 4-HBA dose-dependently suppressed H2O2-induced astrocyte cell death. More specifically, pre-incubation of C6 cells (an astrocyte cell line) with 100 µM 4-HBA for 6 hrs increased survival when cells were treated with H2O2 (100 µM, 1 hr) from 54.2±0.7% to 85.9±1.5%. In addition, 4-HBA was found to up-regulate and activate Nrf2, and subsequently, to induce the expressions of several anti-oxidative genes, such as, HO-1, NQO1, and GCLM. Notably, HO-1 was induced by 3.4-fold in 4-HBA-treated C6 cells, and siRNA-mediated HO-1 knockdown demonstrated that Nrf2 activation and HO-1 induction were responsible for the observed cytoprotective effect of 4-HBA. ERK and Akt signaling pathways were activated by 4-HBA in C6 cells, suggesting their involvements in protective effect of 4-HBA. In addition, 4-HBA-conditioned astrocyte culture medium was found to have neuroprotective effects on primary neuronal cultures or fresh C6 cells exposed to oxidative stress, and these effects seemed to be mediated by glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), which both accumulated in 4-HBA-treated astrocyte culture media. Thus, the 4-HBA-mediated activation of Nrf2 and induction of HO-1 in astrocytes were found to act via autocrine and paracrine mechanisms to confer protective effects. Furthermore, given the pleiotropic effects of 4-HBA with respect to its targeting of various brain cell types and functions, it would appear that 4-HBA has therapeutic potential for the prevention and amelioration of various brain diseases. |
[Mh] Termos MeSH primário: |
Antioxidantes/farmacologia Astrócitos/efeitos dos fármacos Álcoois Benzílicos/farmacologia Morte Celular/efeitos dos fármacos Fármacos Neuroprotetores/farmacologia Estresse Oxidativo/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Animais Antioxidantes/química Astrócitos/citologia Astrócitos/metabolismo Álcoois Benzílicos/química Células Cultivadas Feminino Gastrodia/química Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo Heme Oxigenase-1/metabolismo Peróxido de Hidrogênio/metabolismo Sistema de Sinalização das MAP Quinases/efeitos dos fármacos Camundongos Camundongos Endogâmicos ICR Fator 2 Relacionado a NF-E2/metabolismo Fármacos Neuroprotetores/química Proteínas Proto-Oncogênicas c-akt/metabolismo Regulação para Cima/efeitos dos fármacos Fator A de Crescimento do Endotélio Vascular/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antioxidants); 0 (Benzyl Alcohols); 0 (Glial Cell Line-Derived Neurotrophic Factor); 0 (NF-E2-Related Factor 2); 0 (Neuroprotective Agents); 0 (Vascular Endothelial Growth Factor A); 1A3AH1FP1B (4-hydroxybenzyl alcohol); BBX060AN9V (Hydrogen Peroxide); EC 1.14.14.18 (Heme Oxygenase-1); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 170908 |
[Lr] Data última revisão:
| 170908 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170511 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0177322 |
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