title: Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action.
abstract: BACKGROUND
  Butea superba (BS) is a Thai medicinal plant that has been used as a folk medicine to improve physical and mental conditions and to prevent impaired sexual performance in middle-aged or elderly males. We have previously reported that this plant extract could improve cognitive deficits and depression-like behavior in olfactory bulbectomized mice, an animal model of dementia and depression.
  
  
  OBJECTIVE
  In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect.
  
  
  METHODS
  UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression-like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms. UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP-responsive element binding protein (CREB) and a phosphorylated form of N-methyl-d-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities.
  
  
  CONCLUSIONS
  These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by restoring dysfunctions of the HPA axis and synaptic plasticity-related signaling systems and neurogenesis in the hippocampus.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Daishu
authors.initials: D
authors.lastname: Mizuki
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Electronic address: mkinzo@inm.u-toyama.ac.jp.
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Xoan
authors.initials: X
authors.lastname: Thi Le
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Pharmaceutical Sciences, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Material Development Laboratories, Shiratori Pharmaceutical Co. Ltd., 6-11-24 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D031290:Butea; D050882:CREB-Binding Protein / Q000378:metabolism; D002908:Chronic Disease; D003345:Corticosterone / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000096:biosynthesis; D013315:Stress, Psychological / Q000188:drug therapy*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010936:Plant Extracts; D012333:RNA, Messenger; D050882:CREB-Binding Protein; D003345:Corticosterone
keywords: Butea superba; Depression-like symptoms; Neurogenesis; Synaptic plasticity-related signaling; Unpredictable chronic mild stress