Wild Ginseng Attenuates Repeated Morphine-Induced Behavioral Sensitization in Rats

( Bom Bi Lee ),( Sun Oh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.7

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.

Ginsenoside Rg3 Alleviates Lipopolysaccharide-Induced Learning and Memory Impairments by Anti-Inflammatory Activity in Rats

( Bom Bi Lee ),( Bong Jun Sur ),( Jin Hee Park ),( Sung Hun Kim ),( Sunoh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.5

The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and infl ammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinfl ammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic infl ammation and produced defi cits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration signifi cantly decreased expression of pro-infl ammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these fi ndings suggest that GRg3 signifi cantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-infl ammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer`s disease, by improving cognitive and memory functions due to its anti-infl ammatory activity in the brain.

Chronic Administration of Catechin Decreases Depression and Anxiety-Like Behaviors in a Rat Model Using Chronic Corticosterone Injections

( Bom Bi Lee ),( Bong Jun Sur ),( Sun Oh Kwon ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.4

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confi rmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration signifi cantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and signifi cantly blocked increases of TH expression in the locus coeruleus (LC). It also signifi cantly enhanced the total number of line crossing in the open-fi eld test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these fi ndings indicate that the administration of CTN prior to high-dose exogenous CORT signifi cantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.

L-Tetrahydropalmatine Ameliorates Development of Anxiety and Depression-Related Symptoms Induced by Single Prolonged Stress in Rats

( Bom Bi Lee ),( Bong Jun Sur ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.3

Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitaryadrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.

Erratum : Erratum to "L-Tetrahydropalmatine Ameliorates Development of Anxiety and Depression-Related Symptoms Induced by Single Prolonged Stress in Rats" [Biomol. Ther. 22 (2014) 213-222]

( Bom Bi Lee ),( Bong Jun Sur ),( Mi Jung Yeom ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.5

Bupleurum falcatum Prevents Depression and Anxiety-Like Behaviors in Rats Exposed to Repeated Restraint Stress

( Bom Bi Lee ),( Hye Yeon Yun ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.3

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxietylike behaviors and alters the expression of corticotrophinreleasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamicpituitary- adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

Effect of Ginsenoside Re on Depression- and Anxiety-Like Behaviors and Cognition Memory Deficit Induced by Repeated Immobilization in Rats

( Bom Bi Lee ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.5

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stressinduced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced openarm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

Phellodendron amurense and Its Major Alkaloid Compound, Berberine Ameliorates Scopolamine-Induced Neuronal Impairment and Memory Dysfunction in Rats

Lee, Bom-Bi,Sur, Bong-Jun,Shim, In-Sop,Lee, Hye-Jung,Hahm, Dae-Hyun The Korean Society of Pharmacology 2012 The Korean Journal of Physiology & Pharmacology Vol.16 No.2

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

Wild Ginseng Attenuates Anxiety- and Depression-Like Behaviors During Morphine Withdrawal

( Bom Bi Lee ),( Hyuk Kim ),( In Sop Shim ),( Hye Jung Lee ),( Dae Hyun Hahm ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.10

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety- and depression-like behaviors and expression of corticotrophinreleasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety- and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxietyand depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.

Protective effect of Phellodendri Cortex against lipopolysaccharide-induced memory impairment in rats

Lee, Bom-Bi,Sur, Bong-Jun,Cho, Se-Hyung,Yeom, Mi-Jung,Shim, In-Sop,Lee, Hye-Jung,Hahm, Dae-Hyun The Korean Society for Integrative Biology 2012 Animal cells and systems Vol.16 No.4

The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain.