Uwhangchungsimwon, A Standardized Herbal Drug, Exerts an Anti-Depressive Effect in a Social Isolation Stress-Induced Mouse Model

Frontiers in Pharmacology

Seo-Woo Kim¹  Hyeon-Muk Oh¹  Young-Taeck Oh¹  Yoo-Jin Jeon²  Sung-Bae Lee²  Jin-Seok Lee²  Chang-Gue Son²  Jung-Hyo Cho²  Yong-Rae Cho²  Won-Yong Kim² 

[1] College of Korean Medicine, Daejeon University, Daejeon, South Korea;Liver and Immunology Research Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, South Korea;

关键词: herbal medicine;    Uwhangchungsimwon;    depression;    5-HT;    brain-derived neurotrophic factor;   

DOI  :  10.3389/fphar.2019.01674

来源: DOAJ

【 摘 要 】

IntroductionUwhangchungsimwon (UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms.MethodsA social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum corticosterone level was measured with its receptor and catecholamine, along with cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus.ResultsSocial isolation stress effectively induced depressive-like behaviors, and UCW treatment significantly improved the symptoms of depressive-like behavior in the FST, TST, and OFT. The isolation stress-induced depletion of 5-HT was significantly ameliorated by UCW treatment. UCW also attenuated the activation of the glucocorticoid receptor (GR) and the elevated serum corticosterone level, as well as the hippocampal levels of dopamine and norepinephrine. Dexametasone-derived translocation of GR was inhibited by UCW treatment in PC12 cells and HT22 cells. In addition, alterations of tryptophan hydroxylase 2 (TPH2), BDNF, and CREB in the protein analyses were notably regulated by UCW treatment.ConclusionsThese results provide animal-based evidence for the anti-depressive effect of UCW, and its underlying mechanisms may involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin.

【 授权许可】

Unknown