Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

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Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

Molecules ◽

10.3390/molecules24244587 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4587 ◽

Cited By ~ 2

Author(s):

Juthamart Maneenet ◽

Supawadee Daodee ◽

Orawan Monthakantirat ◽

Chantana Boonyarat ◽

Charinya Khamphukdee ◽

...

Keyword(s):

Oral Administration ◽

Aerial Part ◽

Hplc Analysis ◽

Centella Asiatica ◽

Chronic Mild Stress ◽

Dry Weight ◽

Piper Nigrum ◽

Mild Stress ◽

Herbal Formula ◽

Unpredictable Chronic Mild Stress

Thai traditional herbal formula ‘’Kleeb Bua Daeng (KBD)’’consists of a 1:1:1 ratio (dry weight) of three medicinal plants: Piper nigrum fruit, the aerial part of Centella asiatica and the petals of Nelumbo nucifera. Oral administration of KBD to unpredictable chronic mild stress (UCMS) mice significantly improved their cognitive function caused by chronic mild stress. Daily administration of KBD significantly decreased the serum corticosterone (CORT) and malondialdehyde (MDA) levels but increased the catalase and superoxide dismutase activities in both frontal cortex and hippocampus. The effects of KBD were similar to those caused by oral administration of vitamin E. HPLC analysis of the KBD extract revealed the presence of piperine, madecassoside, asiaticoside, luteolin-7-O-glucoside, rutin, kaempferol-3-glucoside, quercetin, kaempferol and ferulic acid as major constituents.

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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

Molecules ◽

10.3390/molecules24183396 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3396 ◽

Cited By ~ 4

Author(s):

Daodee ◽

Monthakantirat ◽

Ruengwinitwong ◽

Gatenakorn ◽

Maneenet ◽

...

Keyword(s):

Corticosterone Level ◽

Ethanol Extract ◽

Chronic Mild Stress ◽

Tail Suspension Test ◽

Selective Inhibition ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress ◽

Immobility Time ◽

Dipterocarpus Alatus

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.

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Improvement of penile neurogenic and endothelial relaxant responses by chronic administration of resveratrol in rabbits exposed to unpredictable chronic mild stress

International Journal of Impotence Research ◽

10.1038/s41443-018-0016-8 ◽

2018 ◽

Vol 30 (4) ◽

pp. 163-170 ◽

Cited By ~ 2

Author(s):

Yusufhan Yazir ◽

Tijen Utkan ◽

Tuğçe Demirtaş Şahin ◽

Semil Selcen Gocmez

Keyword(s):

Chronic Mild Stress ◽

Chronic Administration ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress

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Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis

Psychopharmacology ◽

10.1007/s00213-017-4720-8 ◽

2017 ◽

Vol 234 (22) ◽

pp. 3385-3394 ◽

Cited By ~ 34

Author(s):

Hong-Yan Li ◽

Ying-Hua Zhao ◽

Min-Jie Zeng ◽

Fang Fang ◽

Min Li ◽

...

Keyword(s):

Hpa Axis ◽

Chronic Mild Stress ◽

Hippocampal Neurogenesis ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress

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Effects of Repeated Citalopram Treatments on Chronic Mild Stress-Induced Growth Associated Protein-43 mRNA Expression in Rat Hippocampus

Korean Journal of Physiology and Pharmacology ◽

10.4196/kjpp.2008.12.3.117 ◽

2008 ◽

Vol 12 (3) ◽

pp. 117 ◽

Cited By ~ 5

Author(s):

Sang-Ha Park ◽

Song-hyen Choi ◽

Jimin Lee ◽

Seungwoo Kang ◽

You-Chan Shin ◽

...

Keyword(s):

Mrna Expression ◽

Chronic Mild Stress ◽

Rat Hippocampus ◽

Mild Stress

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Unpredictable Chronic Mild Stress Paradigm Established Effects of Pro- and Anti-inflammatory Cytokine on Neurodegeneration-Linked Depressive States in Hamsters with Brain Endothelial Damages

Molecular Neurobiology ◽

10.1007/s12035-016-0171-1 ◽

2016 ◽

Vol 54 (8) ◽

pp. 6446-6458 ◽

Cited By ~ 3

Author(s):

Ennio Avolio ◽

Gilda Fazzari ◽

Maria Mele ◽

Raffaella Alò ◽

Merylin Zizza ◽

...

Keyword(s):

Inflammatory Cytokine ◽

Chronic Mild Stress ◽

Mild Stress ◽

Unpredictable Chronic Mild Stress ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine ◽

Depressive States

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Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

PLoS ONE ◽

10.1371/journal.pone.0020955 ◽

2011 ◽

Vol 6 (6) ◽

pp. e20955 ◽

Cited By ~ 58

Author(s):

Xian-cang Ma ◽

Dong Jiang ◽

Wen-hui Jiang ◽

Fen Wang ◽

Min Jia ◽

...

Keyword(s):

Social Isolation ◽

Chronic Mild Stress ◽

Mild Stress ◽

Male Mice ◽

Unpredictable Chronic Mild Stress

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Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0028 ◽

2019 ◽

Vol 17 (2) ◽

Cited By ~ 1

Author(s):

Karima A. El-Shamy ◽

Khaled M. M. Koriem ◽

Nevein N. Fadl ◽

Marwa H. A. El-Azma ◽

Mahmoud S. S. Arbid ◽

...

Keyword(s):

Cerebral Cortex ◽

Oral Intake ◽

Chronic Mild Stress ◽

Preference Test ◽

Tail Suspension Test ◽

Psychiatric Disease ◽

Albino Rats ◽

Mild Stress ◽

Immobility Time ◽

Antioxidant Effects

AbstractBackgroundDepression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms.MethodsThis research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks.ResultsThe sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues.ConclusionsGeranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

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Geranium oil and anise oil inhibit brain cerebral cortex and hippocampus inflammation in depressed animal model

Nutrition & Food Science ◽

10.1108/nfs-05-2020-0159 ◽

2020 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Khaled Mohamed Mohamed Koriem ◽

Nevein Naim Fadl ◽

Salwa Refat El-Zayat ◽

Eman Nasr Hosny ◽

Karima Abbas El-Shamy ◽

...

Keyword(s):

Animal Model ◽

Cerebral Cortex ◽

Psychiatric Disease ◽

Mild Stress ◽

Gamma Aminobutyric Acid ◽

Ki 67 ◽

Necrosis Factor Alpha ◽

Content Type ◽

Anti Inflammatory ◽

Inflammatory Effect

Purpose The purpose of this paper is to check the geranium oil and anise oil effect to inhibit inflammation in brain cerebral cortex and hippocampus areas in depression. Design/methodology/approach Depression defined as psychiatric disease and chronic mild stress (CMS) model a well-known animal model of depression that represented major symptoms occurred in human depression. Geranium oil and anise oil selected for such a study to check their anti-inflammatory effect in brain tissues in depressed animal model. Findings The brain cerebral cortex and hippocampus neurotransmitters serotonin, dopamine, norepinephrine, gamma aminobutyric acid (GABA) and interleukin (IL)-10 significantly decreased (p < 0.001) while brain cerebral cortex and hippocampus IL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α) and Ki-67 levels significantly increased (p < 0.001) in CMS rats compared to control. The oral intake of venlafaxine drug, anise oil and geranium oil significantly increased (p < 0.001) serotonin, dopamine, norepinephrine, GABA and IL-10 while significantly decreased (p < 0.001) IL-1ß, IL-6, TNF-α and Ki-67 levels to approach normal levels in brain cerebral cortex and hippocampus areas compared with CMS rats. Originality/value Antidepressants used in depression treatment but these drugs are either too expensive or had side effects. Folklore and complementary medicine used in different diseases treatment due to cheap and available source. Geranium oil and anise oil had anti-inflammatory effect in brain cerebral cortex and hippocampus areas in CMS rats.

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