Anxiolytic-Like Effects of Ginsenosides on the Elevated Plus-Maze Model in Mice

Cha, Hwa-Young,Park, Jeong-Hill,Hong, Jin-Tae,Yoo, Hwan-Soo,Song, Sukgil,Hwang, Bang-Yeon,Eun, Jae-Soon,Oh, Ki-Wan Pharmaceutical Society of Japan 2005 Biological & pharmaceutical bulletin Vol.28 No.9

<P>In a previous study, we reported that ginseng extract has anxiolytic-like effects in the elevated plus-maze model and that the ginseng saponin fraction plays an important role. This experiment was performed to investigate the anxiolytic-like effects of ginsenosides Rb<SUB>1</SUB>, Rg<SUB>1</SUB>, Rg<SUB>3</SUB>-R, and Rg<SUB>3</SUB>-S, and the Rg<SUB>5</SUB> and Rk mixture isolated from the ginseng saponin fraction in the elevated plus-maze. Furthermore, the anxiolytic-effects of Rb<SUB>1</SUB>, Rg<SUB>1</SUB>, Rg<SUB>3</SUB>-R, Rg<SUB>3</SUB>-S, and the Rg<SUB>5</SUB> and Rk mixture were compared with those of a well-known active anxiolytic drug (diazepam). The oral administration of ginsenoside Rb<SUB>1</SUB> significantly increased the number of open arm entries and the time spent on the open arm compared with those in the vehicle-treated group. Ginsenoside Rg<SUB>1</SUB> and the Rg<SUB>5</SUB> and Rk mixture also significantly increased the number of open arm entries and the time spent on the open arm. However, ginsenosides Rg<SUB>3</SUB>-R and Rg<SUB>3</SUB>-S did not increase the number of open arm entries or the time spent on the open arm. On the other hand, ginsenoside Rb<SUB>1</SUB> and the Rg<SUB>5</SUB> and Rk mixture decreased locomotor activity in a manner similar to diazepam. These data indicate that ginsenosides Rb<SUB>1</SUB>, Rg<SUB>1</SUB>, and the Rg<SUB>5</SUB> and Rk mixture have anxiolytic-like effects, but ginsenosides Rg<SUB>3</SUB>-R and Rg<SUB>3</SUB>-S do not in this model. We provide evidence that some ginsenosides may be useful for the treatment of anxiety.</P>

Anxiolytic-Like Effects of Chrysanthemum indicum Aqueous Extract in Mice: Possible Involvement of GABAA Receptors and 5-HT1A Receptors

( Sa Ik Hong ),( Seung Hwan Kwon ),( Min Jung Kim ),( Shi Xun Ma ),( Je Won Kwon ),( Seung Min Choi ),( Soo Im Choi ),( Sun Yeou Kim ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.4

Chrysanthemum indicum Linne is an ancient herbal medicine used to treat bone and muscle deterioration, ocular infl ammation, headache, and anxiety in Korea, China, and Japan. Furthermore, tea derived from Chrysanthemum indicum Linne has been used to treat anxiety by facilitating relaxation and curing insomnia. However, no reports exist on the anxiolytic-like effects of Chrysanthemum indicum Linne water extract (CWE) in mice. In the present study, we investigated the anxiolytic-like effects of CWE using the elevated plus-maze (EPM) test in mice. CWE, at a dose of 500 mg/kg (p.o.), signifi cantly increased the time spent in the open arms of the EPM compared to a vehicle-injected control group. Moreover, the effect of CWE (500 mg/kg) was blocked by bicuculline (a selective GABAA receptor antagonist) and WAY 100635 (a selective 5-HT1A receptor antagonist). Taken together, these fi ndings suggest that the anxiolytic-like effects of CWE might be mediated by the GABAA receptor and the 5-HT1A receptor.

Milk Collected at Night Induces Sedative and Anxiolytic-Like Effects and Augments Pentobarbital-Induced Sleeping Behavior in Mice

Irene Joy I. dela Peña,홍은영,DELAPENAJUNEBRYAN,김희진,Chrislean Jun Botanas,홍예슬,황예슬,문병석,정재훈 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.11

Milk has long been known and used to promote sleep. The sleep-promoting effect of milk has been attributed to its psychological associations (i.e., the memory of a mother giving milk at bedtime) and its rich store of sleep-promoting constituents (e.g., tryptophan). Studies have shown that milk harvested at night (Night milk) contains exceptionally high amounts of tryptophan and melatonin. In the present study, we evaluated the psychopharmacological properties of Night milk, particularly its probable sleep-promoting/enhancing, and anxiolytic effects. Night milk was orally administered to ICR mice at various concentrations (100, 200, or 300mg/kg). An hour after administration, assessment of its sedative (open-field and rotarod tests) and sedative sleep-potentiating effects (pentobarbital-induced sleeping test) was conducted. For comparison, the effects of Day milk (daytime milking) were also assessed. In addition, the effects of Night milk on anxiety behavior (elevated plus maze [EPM] test) and electroencephalographic (EEG) waves were evaluated. Night milk-treated animals exhibited decreased spontaneous locomotion (open-field test) and impaired motor balance and coordination (rotarod test). Furthermore, Night milk shortened the sleep onset and prolonged the sleep duration induced by pentobarbital sodium. These effects were comparable to that of diazepam. In addition, Night milk significantly increased the percentage of time spent and entries into the open arms of the EPM, indicating that it also has anxiolytic effects. No significant changes in EEG waves were observed. Altogether, these findings suggest that Night milk is a promising natural aid for sleep- and anxiety-related disturbances.

Anxiolytic-like effects of sinapic acid in mice

Yoon, Byung Hoon,Jung, Ji Wook,Lee, Jong-Ju,Cho, Young-Wuk,Jang, Choon-Gon,Jin, Changbae,Oh, Tae Hwan,Ryu, Jong Hoon WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2007 東西醫學硏究所 論文集 Vol.2007 No.-

Sinapic acid is a phenylpropanoid compound and is found in various herbal materials and high-bran cereals. With the exception of its anlioxidant activities, the pharmacological properties of sinapic acid have been rarely reported. The purpose of this study was to characterize the putative anxiolytic-like properties of sinapic acid using an elevated plus-maze (EPM) and hole-board test. Conlrol mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). Sinapic acid (4 ing/kg, P.o.) significantly increased the percentages of time spent in the open arms of the EPM test (P<0.05). In the hole-board test, sinapic acid also significantly increased the number ot head-dips at 4 mg/kg (P<0.05). In addition, the anxiotytic-like properties of sinapic acid examined in the EPM test were blocked by flumazenil or bicuculline, which are GABA_(A) antagonists. Moreover, sinapic acid markedly potentiated GABA current in single cortical neurons in a dose-dependant manner, and reactive I_(GABA) increased to 1.8 times at 1 μM of sinapic acid. These results suggested that sinapic acid is a prominent anxiolytic agent, and that its anxiolytic-like effects are mediated via GABA_(A) receptors and potentiating CI currents.

Anxiolytic-Like Effects of 4-O-Methylhonokiol Isolated from Magnolia officinalis Through Enhancement of GABAergic Transmission and Chloride Influx

Huishan HAN,정재경,한상배,남상윤,오기완,홍진태 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.7

This study investigated the anxiolytic-like effects of 4-O-methylhonokiol, a neolignan compound of Magnolia officinalis, by using the experimental paradigms of anxiety and compared the results with those of a known anxiolytic, diazepam. A single treatment with 4-O-methylhonokiol (0.1, 0.2, and 0.5 mg/kg, p.o.) or treatment for 7 days (0.5 mg/kg in drinking water) increased the percentage of time spent in the open arms and the number of open arms entries in the elevated plus-maze test. However, the 4-O-methylhonokiol-increased percentage of time spent in the open arm was abolished by treatment with flumazenil, a benzodiazepine receptor antagonist (10 mg/kg). 4-O-Methylhonokiol also increased the number of head dips in the hole-board test, but decreased locomotor activity. Molecular experiments revealed that the α1-subunit of γ-aminobutyric acid (GABA) type A receptors was overexpressed in the cortex of brains of mice after treatment with 4-O-methylhonokiol for 7 days. In addition, 4-O-methylhonokiol also increased chloride influx in cultured cortical cells. It is concluded that 4-O-methylhonokiol may have anxiolytic-like effects and that these effects may be mediated by GABAergic transmission with the increase of Cl– channel opening.

Anxiolytic-like Effects of Methanol Extract of Zizyphi Spinosi Semen in Mice

Han, Hui-Shan,Ma, Yu-An,Eun, Jae-Soon,Hong, Jin-Tae,Oh, Ki-Wan The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. $GABA_{A}$ receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

Anxiolytic Effect of Aconiti Tuber Extract in Elevated Plus-maze Test

Young Bae Kwon 한국실험동물학회 2006 Laboratory Animal Research Vol.22 No.2

Selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors are widely used to treat mood and anxiety disorders. Aconiti tuber (AT) is traditionally used to alleviate the psychological disorders in the Oriental medicine. The purpose of this study was to characterize the putative anxiolytic-like effect of the 'ethanol extract of AT' (ATE) using elevated plus-maze (EPM) in mice. We further evaluated whether ATE had the modulatory property of serotonin and norepinephrine using [³H]paroxetine and [³H]nisoxetine binding assay and [³H]norepinephrine uptake assay. In EPM test, intraperitoneal pretreatment of ATE (1 ㎎/㎏) significantly increased the time spent into the open arms compared with the control group. In addition, ATE inhibited the specific binding of [³Hlnisoxetine (selective ligand for norepinephrine transporter) and [³H] norepinephrine uptake in concentration dependent manner. However, ATE did not show any affinity for serotonin transporters in the [³H]paroxetine binding assay. Therefore, these results suggest that ATE may produce anxiolytic-like effect by the selective modulation of norepinephrine reuptake in the central nervous system.

FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase

Son, Dong Hwee,Doan, Khanh V.,Yang, Dong Joo,Sun, Ji Su,Kim, Seul Ki,Kang, Namju,Kang, Jung Yun,Paik, Ji-Hye,DePinho, Ronald A.,Choi, Yun-Hee,Shin, Dong Min,Kim, Ki Woo Elsevier 2019 clinical and experimental Vol.91 No.-

<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>While leptin has been associated with various psycho-physiological functions, the molecular network in leptin-mediated mood regulation remains elusive.</P> <P><B>Methods</B></P> <P>Anxiolytic behaviors and tyrosine hydroxylase (TH) levels were examined after leptin administration. Functional roles of STAT3 and FoxO1 in regulation of TH expression were investigated using in vivo and in vitro systems. A series of animal behavioral tests using dopaminergic neuron-specific FoxO1 KO (FoxO1 KO<SUP>DAT</SUP>) were performed and investigated the roles of FoxO1 in regulation of mood behaviors.</P> <P><B>Results</B></P> <P>Here, we show that administration of leptin induces anxiolytic-like phenotype through the activation of signal transducer and activator of transcription 3 (STAT3) and the inhibition of forkhead box protein O1 (FoxO1) in dopaminergic (DA) neurons of the midbrain. Specifically, STAT3 and FoxO1 directly bind to and exert opposing effects on tyrosine hydroxylase (TH) expression, where STAT3 acts as an enhancer and FoxO1 acts as a prominent repressor. Accordingly, suppression of the prominent suppressor FoxO1 by leptin strongly increased TH expression. Furthermore, our previous results showed that specific deletion of FoxO1 in DA neurons (FoxO1 KO<SUP>DAT</SUP>) led to a profound elevation of TH activity and dopamine contents. Finally, FoxO1 KO<SUP>DAT</SUP> mice exhibited enhanced leptin sensitivity as well as displayed reduced anxiety- and depression-like behaviors.</P> <P><B>Conclusions</B></P> <P>This work establishes a novel molecular mechanism of mood behavior regulation by leptin and suggests FoxO1 suppression by leptin might be a key for leptin-induced behavioral manifestation in DA neurons.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TH increment by leptin is via STAT3 activation and FoxO1 inhibition in midbrain. </LI> <LI> FoxO1 inhibition by leptin is a key in leptin-induced anxiolytic-like behavior. </LI> <LI> FoxO1 KO<SUP>DAT</SUP> mice showed enhanced leptin sensitivity and anxiolytic-like behavior. </LI> </UL> </P>

Anxiolytic-Like Effects of Methanol Extract of Zizyphi Spinosi Semen in Mice

( Hui Shan Han ),( Yuan Ma ),( Jae Soon Eun ),( Jin Tae Hong ),( Ki Wan Oh ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.3

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. GABAA receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

Anxiolytic-Like Effects of Cyclopeptide Fraction Alkaloids of Zizyphi Spinosi Semen: Possible Involvement of GABA(A) Receptors

Hui Shan Han,Yu An Ma,Jae Soon Eun,Jin Tae Hong,Ki Wan Oh 한국응용약물학회 2008 Biomolecules & Therapeutics(구 응용약물학회지) Vol.16 No.3