Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action

J Ethnopharmacol. 2014 Oct 28;156:16-25. doi: 10.1016/j.jep.2014.08.014. Epub 2014 Aug 23.

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and 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.

Conclusion: 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.

Keywords: Butea superba; Depression-like symptoms; Neurogenesis; Synaptic plasticity-related signaling; Unpredictable chronic mild stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Butea*
  • CREB-Binding Protein / metabolism
  • Chronic Disease
  • Corticosterone / metabolism
  • Hippocampus / metabolism
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Mice
  • Pituitary-Adrenal System / metabolism
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • RNA, Messenger / biosynthesis
  • Stress, Psychological / drug therapy*

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Plant Extracts
  • RNA, Messenger
  • CREB-Binding Protein
  • Corticosterone