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Introduction: Depression is a serious and common mental disease that causes low mood and loss of interest in activities. Nelumbinis semen (NS) has been widely used as a treatment for depression for hundreds of years in many Asian countries. Water extract of nelumbinis semen (WNS) is a standardized herbal medicine made from NS. Methods: The objective of the present research was to perform a randomized, double-blind, placebo-controlled trial to estimate the efficacy of WNS for improving depressive and stress symptoms using Beck depression inventory (BDI) and the stress response inventory (SRI) in 45 adults diagnosed with major depression or other forms of depressive disorders. They were randomized to either a placebo-treated group, a 2.4 g per day WNS-treated group, or a 4.8 g per day WNS-treated group. BDI and SRI were determined in order to evaluate changes in depression before and after two weeks of WNS treatment. Results: The average BDI and SRI of the 2.4 g WNS-treated group were significantly (p < 0.05) improved compared to those of the placebo-treated group. Their BDI subscale A (negative attitudes towards self) and subscale C (somatic disturbances), SRI E, and depression subscale of SRI were substantially shorter (p < 0.05). In addition, an analysis of collected EEG data of participants showed a significant increase in alpha/beta activity in the 4.8 g WNS-treated group, which might be explained as an advancement of their depression symptoms (p < 0.05). Conclusions: These results suggest that WNS treatment can decrease depression. Our study provides preliminary evidence for the safety of WNS and its potential to decrease depression.

Background: Chitoglucan (CG) is a bioactive component obtained from Flammulina velutipes Sing, an edible mushroom, which is known to have an anti-obesity effect. However, its biological and hormonal activities in alleviating obesity through regulation of adipocyte-derived proteins have not been examined yet. Purpose: The present study aimed to investigate the anti-obesity effects of chitoglucan and its hormonal mechanisms in high-fat diet (HFD)-induced mice. Methods: The mice were fed either a normal diet (Normal group) or a high fat diet (HFD group) over 6 weeks. The HFD fed mice were administered with saline (HFD group), adipex (HFD + adipex group), chitoglucan 50, 150, or 300 mg/kg/day for 3 weeks (HFD + CG groups). The food consumption, body weight, fat contents, and the levels of serum leptin and resistin were assessed after treatment of chitoglucan. Results: the HFD produced a marked increase in body and fat weights after 6 weeks of feeding compared with the Normal group. Administration of chitoglucan for 3 weeks tended to reduce body weight and significantly decreased parametrical adipose tissues in HFD groups. The level of serum leptin in the HFD group was markedly higher than that in the Normal group, whereas the level of leptin in the chitoglucan treated groups was significantly decreased in comparison with the HFD group. In addition, the level of serum resistin in high-fat diet group tended to be more increased than Normal group. However, the serum resistin level was significantly reduced in HF diet groups after treatment with chitoglucan (50 mg/kg or 150 mg/kg). Conclusion: Collectively, these data suggest that chitoglucan from the Flammulina velutipes may be useful in the treatment of high diet-induced obesity and metabolic syndrome.

Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative-hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative-hypnotic effects of water extracts of five medicinal plants

BackgroundTrimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice.MethodsCD4+CD25+ Tregs were expanded in vitro and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after mouse sacrifice. To investigate the neuroinflammatory responses, the polarization status of microglia was examined in vivo and in vitro using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assy (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging in vitro with an activation-specific fluorescence probe, CDr20.ResultsAdoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via in vitro live time lapse imaging in a Treg/microglia co-culture system.ConclusionsThese data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization.

Background: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. Methods: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg&middot, kg&minus, 1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. Results: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. Conclusion: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer&rsquo, s disease.

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.

// Hyunjung Baek 1 , Minsook Ye 1 , Geun-Hyung Kang 1 , Chanju Lee 1 , Gihyun Lee 1 , Da Bin Choi 1 , Jaehoon Jung 1 , Hyunseong Kim 2 , Seonhwa Lee 3 , Jin Su Kim 3 , Hyun-ju Lee 4 , Insop Shim 4 , Jun-Ho Lee 5 and Hyunsu Bae 1 1 Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea 2 K-herb Research Center, Korea Institute of Oriental Medicine, Yuseongdae-ro, Yuseong-gu, Daejeon, Republic of Korea 3 Division of RI Research, Korea Institute of Radiological & Medical Sciences University of Science & Technology, Gongneug-dong, Nowon-ku, Seoul, Republic of Korea 4 Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, Seoul, Republic of Korea 5 Department of Biotechnology, Chonnam National University, Gwangju, Republic of Korea Correspondence to: Hyunsu Bae, email: // Keywords : Alzheimer’s disease, regulatory T cells (Treg), amyloid-beta (Aβ) pathology, Immunology and Microbiology Section, Immune response, Immunity Received : July 23, 2016 Accepted : September 29, 2016 Published : October 04, 2016 Abstract Alzheimer’s disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer’s disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer’s disease progression. First, we explored the effect of Tregs (CD4 + CD25 + T cells) and Teffs (CD4 + CD25 - T cells) in an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs diminished behavioral function and cytokine production. Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61). Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with 18 F-2 fluoro-2-deoxy-D-glucose ([F- 18 ] FDG) neuroimaging. Importantly, the deposition of Aβ plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer’s disease treatment.

Parkinson’s disease (PD) is a progressive degenerative disorder of the central nervous system (CNS) that leads to impairment of motor skills and speech. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the dopaminergic (DA) neurons, and 1-4-Methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the microglia cells that produced reactive oxygen species (ROS). We recently reported that Ligustri Fructus (LF), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of LF (0.01, 5, 10 ug) on the neurotoxicity of MPTP in mice and on the MPP + -induced cell death in differentiated PC12 cells. In vivo experiment, MPTP injection revealed a significant loss of DA neurons in the substantia nigra, while LF (100, 200 mg/ kg) treatment dramatically reversed DA neuron loss in immunohistochemistry assay for tyrosine hydroxylase (TH). Furthermore, LF attenuated the MPP + -induced cell death, decreased the generation of ROS, and activated glutathione peroxidase in PC12 cells. These results suggest that LF may be beneficial for the treatment of neurodegenerative diseases such as PD.

Foxp3-expressing CD4+ regulatory T cells (Tregs) are vital for maintaining immune tolerance in animal models of various immune diseases. In the present study, we demonstrated that bee venom phospholipase A2 (bvPLA2) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. We associated this neuroprotective effect of bvPLA2 with microglial deactivation and reduction of CD4+ T cell infiltration. Interestingly, bvPLA2 had no effect on mice depleted of Tregs by injecting anti-CD25 Ab. This finding indicated that Treg-mediated modulation of peripheral immune tolerance is strongly involved in the neuroprotective effects of bvPLA2. Furthermore, our results showed that bvPLA2 directly bound to CD206 on dendritic cells and consequently promoted the secretion of PGE2, which resulted in Treg differentiation via PGE2 (EP2) receptor signaling in Foxp3−CD4+ T cells. These observations suggest that bvPLA2-CD206-PGE2-EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson’s disease.

Background Alzheimer׳s disease (AD) is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. This study investigated whether treatment with standardized Lycii Fructus Extract (LFE) would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. Ethnopharmacological relevance Lycii Fructus is a fruit of Lycium chinense Miller and widely distributed in East Asia and has been used traditionally for anti-aging purposes. Materials and methods The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test. The levels of the amyloid beta deposits and NeuN in the hippocampus were evaluated with immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. Results LFE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. In addition, LFE significantly decreased Aβ deposits, increased NeuN-positive cells, and upregulated the expression of BDNF and TrkB in the 3xTg AD mice. Conclusions The present study suggests that LFE treatment can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.

Parkinson’s disease (PD) involves the neurodegeneration of dopaminergic neurons, which is accompanied by neuroinflammation in the substantia nigra (SN). Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit microglial activation-induced inflammation as well as DA neuronal damage. In this study, treatment with Pogostemon Cabin (PC) prevented the degeneration of the Dopamine (DA) neurons in the substantia nigra (SN). This neuro-protective effect of PC was associated with microglial deactivation and a reduction in CD4+ T cell infiltration. Therefore, the results of this study suggest that PC exerts its neuroprotective function via its anti-inflammatory properties and that PC could be employed as a novel therapeutic agent for PD associated with neuroinflammation and CD4+ T cell infiltration into central nerve system.

Background: Alzheimer's disease (AD) is a severe neuroinflammatory disease. CD4(+) Foxp3(+) regulatory T cells (Tregs) modulate various inflammatory diseases via suppressing Th cell activation. There are increasing evidences that Tregs have beneficial roles in neurodegenerative diseases. Previously, we found the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro. Methods: To examine the effects of bvPLA2 on AD, bvPLA2 was administered to 3xTg-AD mice, mouse model of Alzheimer's disease. The levels of amyloid beta (A beta) deposits in the hippocampus, glucose metabolism in the brain, microglia activation, and CD4(+) T cell infiltration were analyzed to evaluate the neuroprotective effect of bvPLA2. Results: bvPLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of A beta deposits in the hippocampus were dramatically decreased by bvPLA2 treatment. This neuroprotective effect of bvPLA2 was associated with microglial deactivation and reduction in CD4(+) T cell infiltration. Interestingly, the neuroprotective effects of bvPLA2 were abolished in Treg-depleted mice. Conclusions: The present studies strongly suggest that the increase of Treg population by bvPLA2 treatment might inhibit progression of AD in the 3xTg AD mice.

Alzheimer’s disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. This study investigated whether treatment with the herbal formula PM012 would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test and positron-emission tomography (PET) with 18 F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. The levels of the amyloid beta (Aβ) deposits in the hippocampus were evaluated by immunohistochemistry. Neurogenesis was assessed by quantitative labeling with the DNA marker bromodeoxyuridine (BrdU) and the newborn neuron marker doublecortin (DCX). PM012 treatment significantly ameliorated memory deficit in AD mice, as shown by shortened escape latencies and increased time spent in the target zone during probe tests. In addition, PM012 significantly decreased Aβ deposits, up-regulated the expression of brain-derived neurotrophic factor (BDNF), increased neurogenesis, and improved brain glucose metabolism in the 3xTg-AD mice. These results suggest that PM012 could be a promising treatment for AD.

Parkinson’s disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP+) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain’s immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD.

α-Synuclein (α-Syn) has a critical role in microglia-mediated neuroinflammation, which leads to the development of Parkinson's disease (PD). Recent studies have shown that bee venom (BV) has beneficial effects on PD symptoms in human patients or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin-induced PD mice. This study investigated whether treatment with BV-derived phospholipase A2 (bvPLA2) would improve the motor dysfunction and pathological features of PD in human A53T α-Syn mutant transgenic (A53T Tg) mice. The motor dysfunction of A53T Tg mice was assessed using the pole test. The levels of α-Syn, microglia and the M1/M2 phenotype in the spinal cord were evaluated by immunofluorescence. bvPLA2 treatment significantly ameliorated motor dysfunction in A53T Tg mice. In addition, bvPLA2 significantly reduced the expression of α-Syn, the activation and numbers of microglia, and the ratio of M1/M2 in A53T Tg mice. These results suggest that bvPLA2 could be a promising treatment option for PD.

Alzheimer’s disease (AD) is the most prevalent cause of dementia marked by progressive cognitive and functional impairment and memory loss. AD patients display neuropathological lesions including deposition of extracellular amyloid-beta (Aβ) peptide and the formation of neurofibrillary tangles. Although the mechanisms causing brain atrophy and neuronal death are largely unknown, increasing evidence suggests that immunity plays a critical role in the pathogenesis of AD. In the present study, we investigated the effect of regulatory T cells (Tregs) on AD mouse model. First, we transiently depleted Treg population using anti-CD25 antibody. Depletion of Tregs for 4 months resulted in a marked aggravation of the spatial learning deficits of 6-month-old 3xTg-AD mice. Importantly, deposition of Aβ plaques and CD11b+ microglia/macrophage were significantly increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Next, we explored the effect of Teffs (effector T cells; CD4+CD25−) and Treg (CD4+CD25+) in adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs showed increased Aβ plaques burden and diminished behavioral function. Our finding strongly suggested that systemic Treg administration ameliorates disease progression and could be an effective AD treatment.

Alzheimer’s disease (AD) is the most common form of dementia and characterized by an imbalance between the production and clearance of amyloid-beta (Aβ) and tau proteins. Vaccination against Aβ peptide results in dramatic reduction of Aβ pathology in experimental mouse models. Our recent study demonstrated that bvPLA2, the major component of BV, causes immune tolerance by increasing the population of CD4+CD25+Foxp3+ Tregs in cisplatin-induced nephrotoxicity, an allergic asthma and Parkinson disease murine model. Here, we investigated that the effect of bvPLA2 to induce antigen-specific Tregs to ameliorate Alzheimer’s disease (AD) pathology through linked immunosuppression. First, we investigated whether bvPLA2 would improve the cognitive function and the pathological features of AD in Aβ-vaccinated-3xTg-AD mice. bvPLA2 treatment dramatically ameliorated learning and memory deficits in Aβ-vaccinated-AD mice. In addition, bvPLA2 significantly reduced Aβ deposits in the hippocampus and cortex region of AD mice, compared with the Aβ-vaccinated-AD mice group. Next, we systemically administered Aβ-specific Treg populations generated in the absence or presence of bvPLA2 into 3xTg-AD mice. Systemic transplantation of Aβ-specific Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. Furthermore, adoptive transfer of Tregs generated in the presence of bvPLA2 showed reduced Aβ plaques and diminished learning and memory ability compared with Tregs generated in the absence of bvPLA2. This opens the possibility of new therapeutic strategy to target Tregs to tissue-specific antigens for the treatment of AD.

Background: Many studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas. Paecilomyces japonica (PJ) is a herbal medicine that is commonly used to treat opiate and other addictions in Eastern Asia. However, its influence on nicotine addiction has not been examined. This study was carried out to investigate the effects of PJ on repeated nicotine-induced behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Methods: Rats were pretreated with PJ (10, 25, 50, 100, and 200 mg/kg, intraperitoneally) 30 min before repeated injections of nicotine (0.4 mg/kg, subcutaneously, twice daily for 7 days). Locomotor activity was measured in rats during 7-day nicotine treatments. On the seventh day, c-Fos and TH expression were assessed. Results: Pretreatment with PJ decreased the development of nicotine-induced sensitization, c-Fos expression in the nucleus accumbens and striatum, and TH expression in the ventral tegmental area. PJ decreased nicotine-induced locomotor activity by modulating brain dopaminergic systems. Conclusion: The results of the present study suggest that PJ may be a useful agent for preventing and treating nicotine addiction.