Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling

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• 作者：Wei-Cheng Chen^a ; Yi-Syuan Lai^a ; Shih-Hang Lin^a ; Kuan-Hung Lu^a ; Yu-En Lin^a ; Suraphan Panyod^a ; Chi-Tang Ho^b ; Lee-Yan Sheen^a ; ^c ; ^d ; ^{lysheen@ntu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：WGE ; water extracts of Gastrodia elata Bl. ; GAS ; gastrodin ; HBA ; 4-hydroxybenzyl alcohol ; HB ; 4-hydroxybenzyl aldehyde ; VAN ; vanillin ; OFT ; open field test ; FST ; forced swimming test ; MDD ; major depression disorder ; 5-HT ; serotonin ; 5-HIAA ; 5-hydroxyindoleacetic acid ; DA ; dopamine ; DOPAC ; 3 ; 4-dihydroxyphenylacetic acid ; HVA ; homovanillic acid ; CRMP2 ; dihydropyrimidinase-related protein 2 ; RhoA ; Ras homologous member A ; PFN1 ; profilin 1 ; HPLC ; high performance liquid chromatography ; CTL ; control
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：22 April 2016
• 年：2016
• 卷：182
• 期：Complete
• 页码：190-199
• 全文大小：1563 K

文摘

Gastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling.

Materials and methods

Gastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection.

The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5 mg/mL), GAS (50, 100 and 100 μM), and HBA (50, 100 and 100 μM).

Results

Oral administration of WGE (500 mg/kg bw), GAS (100 mg/kg bw), and HBA (100 mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells.

Conclusion

WGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention.