Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 18;24(18):3396.
doi: 10.3390/molecules24183396.

Effects of the Ethanol Extract of Dipterocarpus alatus Leaf on the Unpredictable Chronic Mild Stress-Induced Depression in ICR Mice and Its Possible Mechanism of Action

Supawadee Daodee  1 , Orawan Monthakantirat  2 , Kanlaya Ruengwinitwong  3 , Kankrittanon Gatenakorn  4 , Juthamart Maneenet  5 , Charinya Khamphukdee  6 , Nazim Sekeroglu  7 , Yaowared Chulikhit  8 , Anake Kijjoa  9
Affiliations

Effects of the Ethanol Extract of Dipterocarpus alatus Leaf on the Unpredictable Chronic Mild Stress-Induced Depression in ICR Mice and Its Possible Mechanism of Action

Supawadee Daodee et al. Molecules. .

Abstract

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.

Keywords: Dipterocarpus alatus; HPA axis; MAO-A inhibition; UCMS; depression; flavonoids; neurogenesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effects of the ethanol extract of D. alatus leaf (LE) on the unpredictable chronic mild stress (UCMS)-induced anhedonia behavior in sucrose preference test. The amount of 2% sucrose solution taken by each animal group was measured as an index of anhedonia behavior once a week. Each consumption represents the mean ± S.E.M. (n = 10–12 in each animal group). ## p < 0.001 vs. vehicle-treated non-stress group. * p < 0.05, ** p < 0.001 vs. vehicle-treated UCMS group.
Figure 2
Figure 2
The effect of the ethanol extract of D. alatus leaf (LE) on hopeless behavior using forced swimming test (FST) and tail suspension test (TST). Immobility of each animal group was measured as an index of hopeless behavior 6 weeks after starting unpredictable chronic mild stress (UCMS) procedure. Each column represents the mean ± S.E.M. (n = 10–12 in each animal group). ## p < 0.001 vs. the vehicle-treated non-stress group. ** p < 0.001 vs. the vehicle-treated UCMS group. ¤ p < 0.05 compared between doses of the ethanol extract of D. alatus leaf (LE).
Figure 3
Figure 3
The effect of and the ethanol extract of D. alatus leaf (LE) on the locomotor activity in the Y-maze task. The number of arm entries of each group was determined. Each column represents the mean ± S.E.M. (n = 10–12 in each animal group).
Figure 4
Figure 4
Effects of and the ethanol extract of D. alatus leaf (LE) and imipramine (IMP) on unpredictable chronic mild stress (UCMS)-induced elevation in serum corticosterone (CORT) levels. Each column represents the mean ± S.E.M. (n = 3–5). ## p<0.001 vs. the sham-operated group. * p < 0.05 vs. the vehicle-treated UCMS group.
Figure 5
Figure 5
Effects of and the ethanol extract of D. alatus leaf (LE) on unpredictable chronic mild stress (UCMS)-induced changes in the frontal cortex and hippocampal expression of genes encoding serum- and glucocortoid-inducible kinase 1 (SGK1) (panel A), cyclic AMP-responsive element binding (CREB) (panel B), and brain-derived neurotrophic factor (BDNF) (panel C). Each column represents the mean ± S.E.M. (n = 3–5). * p < 0.05 and ** p < 0.001 vs. the sham-operated group. # p < 0.05, ## p < 0.001 vs. the UCMS group. ¤ p < 0.05 compared between doses of the ethanol extract of D. alatus leaf (LE).
Figure 6
Figure 6
A schematic representation of the experimental protocols. The mice were divided into two main groups, i.e. the non-stress group and the unpredictable chronic mild stress (UCMS) group at week 1. The UCMS group was exposed to various unpredictable stressors from week 1 to week 6. The UCMS group was divided into 4 groups which daily received (i) vehicle, (ii) LE 100 mg/kg, (iii) LE 500 mg/kg, and (iv) IMP 20 mg/kg, from week 4 to week 7. Behavioral test started at week 6 to week 7. One day after the Y-maze task, mice were decapitated to collect the blood and brain for neurochemical analysis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. O’Keane V., Frodl T., Dinan T.G. A review of atypical depression in relation to the course of depression and changes in HPA axis organization. Psychoneuroendocrinology. 2012;37:1589–1599. doi: 10.1016/j.psyneuen.2012.03.009. - DOI - PubMed
    1. Bhutani M.K., Bishnoi M., Kulkarni S.K. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol. Biochem. Behav. 2009;92:39–43. doi: 10.1016/j.pbb.2008.10.007. - DOI - PubMed
    1. Pariante C.M., Lightman S.L. The HPA axis in major depression: Classical theories and new developments. Trends Neurosci. 2008;31:464–468. doi: 10.1016/j.tins.2008.06.006. - DOI - PubMed
    1. Herman J.P., McKlveen J.M., Solomon M.B., Carvalho-Netto E., Myers B. Neural regulation of the stress response: Glucocorticoid feedback mechanisms. Braz. J. Med. Biol. Res. 2012;45:292–298. doi: 10.1590/S0100-879X2012007500041. - DOI - PMC - PubMed
    1. Odaka H., Adachi N., Numakawa T. Impact of glucocorticoid on neurogenesis. Neural Regen. Res. 2017;12:1028–1035. doi: 10.4103/1673-5374.211174. - DOI - PMC - PubMed

MeSH terms

Substances

-