Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model

Abstract Objectives According to the WHO report, depression will be the first of the global burden of diseases in 2030. There is more than fifty % of people suffered from depression and anxiety. However, only less than half of the patients receive appropriate treatments due to its side effects of the antidepressants and anxiolytics. Poria cocos (PC) and Cordyceps militaris (CM) are historically used as a complementary therapy to treat depression and anxiety because of its anti-inflammation ability. Instead of fruiting bodies, C. militaris waster medium (CMWM) is a by-product and containing a higher amount of cordycepin than fruiting bodies. Thus, this study aims to investigate the anti-depressive and anti-anxiety effects of extract formula (PC-CMWM) via the regulation of inflammation pathways. Methods Unpredictable chronic mild stress (UCMS) model was used in this study to induce depression-like and anxiety-like behaviors in rats. The 6 weeks-old male Sprague Dawley rats were divided into five groups: control (CTL), UCMS-vehicle (NCTL), and three PC-CMWM groups (low, medium, and high dosage). The sucrose preference test and elevated plus maze (EPM) were preformed after UCMS for 35 days. The neurotransmitters (serotonin and dopamine) were measured by HPLC. The pro-inflammatory cytokines IL-1β and glutamate in the amygdala and serum were analyzed, and the proteins of p38 MAPK and NF-κB related to inflammation were evaluated by western blotting. Results PC-CMWM reversed the behavioral deficiency induced by UCMS exposure, including body weight loss, food intake, and sucrose preference compared to NCTL group (P < 0.05). In the EPM analysis, rats supplemented with PC-CMWM significantly increased the time spent in open arm than those in NCTL (P < 0.05). Besides, treatment with PC-CMWM significantly reduced glutamate in the amygdala and metabolic of serotonin and dopamine in the prefrontal cortex (P < 0.05) compared with NCTL. PC-CMWM improved the IL-1β in serum and reduced p38 MAPK and NF-κB protein expression in the prefrontal cortex (P < 0.05) compared with that in NCTL rats. Conclusions PC-CMWM exhibited anti-depressive and anxiolytic effects via reducing inflammation and modulating neurotransmitters and it can be used as a functional food to prevent depression and anxiety. Funding Sources TARI1073027.

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Poria cocos water extract ameliorates the behavioral deficits induced by unpredictable chronic mild stress in rats by down-regulating inflammation

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.112566 ◽

2020 ◽

Vol 258 ◽

pp. 112566

Author(s):

Yun-Ju Huang ◽

Nai-Yuan Hsu ◽

Kuan-Hung Lu ◽

Yu-En Lin ◽

Shih-Hang Lin ◽

...

Keyword(s):

Water Extract ◽

Chronic Mild Stress ◽

Mild Stress ◽

Behavioral Deficits ◽

Poria Cocos ◽

Unpredictable Chronic Mild Stress

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Water extract of Armillaria mellea (Vahl) P. Kumm. Alleviates the depression-like behaviors in acute- and chronic mild stress-induced rodent models via anti-inflammatory action

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.113395 ◽

2021 ◽

Vol 265 ◽

pp. 113395

Author(s):

Yu-En Lin ◽

Hsiang-Lan Wang ◽

Kuan-Hung Lu ◽

Yun-Ju Huang ◽

Suraphan Panyod ◽

...

Keyword(s):

Water Extract ◽

Chronic Mild Stress ◽

Mild Stress ◽

Rodent Models ◽

Armillaria Mellea ◽

Anti Inflammatory ◽

Inflammatory Action

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

Pharmaceuticals ◽

10.3390/ph14070659 ◽

2021 ◽

Vol 14 (7) ◽

pp. 659

Author(s):

Juthamart Maneenet ◽

Orawan Monthakantirat ◽

Supawadee Daodee ◽

Chantana Boonyarat ◽

Yutthana Chotritthirong ◽

...

Keyword(s):

Mrna Expression ◽

Chronic Mild Stress ◽

Antidepressant Activity ◽

Piper Nigrum ◽

Psychiatric Disease ◽

Mild Stress ◽

Herbal Formula ◽

Necrosis Factor Alpha ◽

Unpredictable Chronic Mild Stress

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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