Kai-Xin-San Research Articles

Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats.

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg–1·day–1; and oral KXS at a dose of 676 mg·kg–1·day–1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg–1·day–1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg–1·day–1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways.

Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS. In total, 24 male Wistar rats were randomly divided into three groups, including control (n=8, no treatment), induced with chronic unpredictable mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for cell survival and proliferation assays. In KXS rats, increased protein expression levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the hippocampus and prefrontal cortex, compared with the CMS model group. Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3β were also detected in the hippocampus and prefrontal cortex of KXS-treated rats compared with CMS model rats and in primary hippocampal neuronal cells treated with KXS. These results suggest that pCREB and upstream components, including TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect induced by KXS. Further studies are required to confirm these findings.

Identification and determination of the major constituents in Kai-Xin-San by UPLC-Q/TOF MS and UFLC-MS/MS method.

In order to have overall chemical material information of Kai-Xin-San (KXS), the reliable ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UHPLC-Q-TOF-MS) and ultra-fast liquid chromatography mass spectrometer (UFLC-MS/MS) methods were developed for the identification and determination of the major constituents in KXS. Moreover, the UHPLC-Q-TOF-MS method was also applied to screen for multiple absorbed components in rat plasma after oral administration of KXS. The UHPLC-Q-TOF-MS method was achieved on Agilent 6520 Q-TOF mass and operated in the negative ion mode. Good separation was performed on a ZORBAX Eclipse Plus C18 column with a gradient elution at a flow rate of 0.2 ml/min. A total of 92 compounds in KXS were identified or tentatively characterized based on their exact molecular weights, fragmentation patterns, and literature data. A total of 26 compounds including 23 prototype components and three metabolites were identified in rat plasma after oral administration of KXS. Then, 16 major bioactive constituents were chosen as the benchmark substances to evaluate the quality of KXS. Their quantitative analyses were performed by a triple quadrupole tandem mass spectrometer (MS/MS) operating in multiple-reaction monitoring mode(MRM). The analysis was completed with a gradient elution at a flow rate of 0.4 ml/min within 35 min. The simple and fast method was validated and showed good linearity, precision, and recovery. Furthermore, the method was successful applied for the determination of 16 compounds in KXS. All results would provide essential data for identification and quality control of active chemical constituents in KXS. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Kaixinsan on monoamine oxidase activity

To observe the effect of antidepressant medicine prescription, Kaixinsan (KXS) on monoamine oxidase (MAO) activity, and explore the mechanism of KXS in elevating the levels of monoamine neurotransmitter from the perspective of metabolism, in vitro enzyme reaction system and C6 neuroglial cells, the effect of KXS at different concentrations on MAO-A and MAO-B activity was observed. In animal studies, the effect of KXS at different concentrations on MAO-A and MAO-B activities of brain mitochondrialin normal rats and solitary chronic unpredictable moderate stress (CMS) model rats after intragastric administration for 1, 2, 3 weeks. Results showed that 10 g•L⁻¹ KXS could significantly reduce the activity of MAO-A and MAO-B in enzyme reaction system; and in C6 cells, KXS within 0.625-10 g•L⁻¹ concentration range had no significant effect on the activity of MAO-A, but had obvious inhibitory effect on the activity of MAO-B in a dose dependent manner. KXS had no significant effect on the activity of MAO-A and MAO-B in brains of normal rats after action for 1, 2, 3 weeks. After 2 and 3 weeks treatment with 338 mg•kg⁻¹ dose KXS, MAO-A activity in the brain of CMS rats was decreased as compared with the model group (P<0.05), while KXS had no significant effect on MAO-B activity after 1, 2, 3 weeks of treatment. The results indicated that KXS had certain effect on in vitro MAO-A and MAO-B activity, had no effect on brain MAO-A and MAO-B activity in vivo in normal rats, and had certain inhibitory effect on MAO-A activity in brains of CMS rats.

The memory enhancement effect of Kai Xin San on cognitive deficit induced by simulated weightlessness in rats

Ethnopharmacological relevanceIt is vital for astronauts to develop effective countermeasures to prevent their decline of cognitive performance in microgravity to make space-flight missions successful. The traditional Chinese herbal formula Kai Xin San (KXS) has been used to treat amnesia for thousands years. It is a traditional complex prescription comprising of ginseng (Panax ginseng C. A. Meyer), hoelen (Poria cocos (Schw.) Wolf), polygala (Polygala tenaifolia Willd), and acorus (Acorus tatarinowii Schott). Previous study showed KXS could improve CMS-induced memory impairment in rats. Material and methodsIn this paper, a unique environmental factor—microgravity (weightlessness) was simulated as hindlimb suspension (HLS) by tail in rats for two weeks as the HLS animal model. The KXS at the doses of 0.3 or 0.6g/kg p.o. daily was administrated to HLS rats for two weeks at the same time of HLS, the memory behavior tests were investigated with Morris water maze (MWM) and Shuttle Box (SB) test. The levels of ROS, 8-OHdG and 3-nitrotyrosine (3-NT) in the serum, and AChE and ChAT activity in the brain of rats were determined by ELISA or biochemical analysis. ResultsAfter HLS for two weeks, the escape latency and the swimming distance were significantly increased in the MWM test in rats in the HLS group, compared with control group. The percent of swimming distance in target quadrant and the number of target crossing was significantly decreased in rats in the HLS group compared with the control group. Performance in the SB test showed, the numbers and the distance of active avoidance was decreased from day 4 to day 7, the time spent in electric area was increased in rats in the HLS group compared with the control group.Administration of KXS 0.3 or 0.6g/kg to the HLS rats for two weeks significantly reduced the escape latency and the swimming distance, increased the percentage of swimming distance in target quadrant and the number of target crossings (P<0.01, compared with the HLS group) in the MWM test. Similar treatment with KXS increased the numbers and the distance of active avoidance (P<0.01, compared with the HLS group) and reduced the time spent in electric area after training 3 days in the SB test (P<0.01, compared with the HLS group).The HLS induced the increase of the ROS, 8-OHdG and 3-NT in the serum of rats, but has little influence on the AChE, ChAT activity in the brain. Only the AChE activity in the cortex and the ChAT activity in the hippocampus had some changes in rats in the HLS model group.After administration of KXS 0.6g/kg for two weeks, the abnormal levels of ROS, 8-OHdG, 3-NT were found reversed in the serum of rats (P<0.05, compared with HLS model group). And KXS 0.3g/kg was found reversed the increased AChE activity in the cortex. ConclusionsExperimental results from this study show that KXS may improve memory deficiency induced by HLS, its mechanisms are major related to antioxidant activities, rather than the central cholinergic system.

Metabolomics approach to explore the effects of Kai-Xin-San on Alzheimer's disease using UPLC/ESI-Q-TOF mass spectrometry.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that influences elderly populations, with no effective method for its treatment so far. To improve its diagnosis and treatment, changes of small molecule metabolite during AD should be elucidated. Kai-Xin-San (KXS) is an herbal formulae that has been widely used to treat mental disorders, especially amnesia and depression in China. Experimental AD was induced in rats by an intraperitoneal injection of d-galactose (d-gal) and administered intragastrically with aluminum chloride (AlCl3) simultaneously for 105 days. Morris water maze task as a behavior test was used for testing the effects of KXS on AD model and pathological changes to the brain were assessed by hematoxylin-eosin staining and immunohistochemistry. The levels of Bcl-2 and ChAT in hippocampus were evaluated by western-blot. Furthermore, metabolite profiling of AD was performed through ultra-performance liquid chromatography/electrospray ionization quadruple time-of- flight-high-definition mass spectrometry (UPLC/ESI-Q-TOF/HDMS) combined with pattern recognition approaches and pathway analysis. d-gal and AlCl3-treated caused a decline in spatial learning and memory, hippocampal histopathological abnormalities and increased Aβ1-40 levels in the brain cortex and hippocampus along with decreased Bcl-2 and ChAT expression in the hippocampus. KXS significantly improved the cognitive impairment induced by d-gal and AlCl3, attenuated hippocampal histopathological abnormalities, reduced Aβ1-40 levels and increased Bcl-2 and ChAT expression in the hippocampus. A total of 48 metabolites were considered as potential biomarkers of AD, and 36 metabolites may correlate with the regulation of KXS treatment on AD. Changes in AD metabolic profiling were close to normal states through regulating multiple perturbed pathways after KXS treatment. This study has revealed the potential biomarkers and metabolic networks of AD, illuminated the biochemistry mechanism of AD and the metabolic pathways influenced by KXS.

Behavioral and biochemical effects of a formulation of the traditional Chinese medicine, Kai-Xin-San, in fatigued rats

The present study was designed to evaluate the anti-fatigue activity and the behavioral and biochemical effects of Kai-Xin-San (KXS) extracts on fatigued rats. The rats were randomly divided into six groups: untreated control (UC), running control (RC), RC treated with 13 mg/kg/day modafinil and RC treated with KXS at dosages of 125, 250 and 500 mg/kg/day, respectively. The treatments were administered orally. Anti-fatigue activity was assessed using the treadmill running test and serum biochemical parameters were determined using an autoanalyzer and commercially available kits. Furthermore, the standardization of the KXS extracts was ensured using a high-performance liquid chromatography (HPLC)-fingerprint. The extracts were shown to increase exhaustive running time in the treadmill running test and reverse the fatigue-induced reduction in hepatic/muscle glycogen and testosterone, in addition to reducing the lactate dehydrogenase (LDH), serum urea nitrogen (SUN), blood lactic acid (BLA) and β-endorphin levels in the serum of the fatigued rats. Moreover, the extracts enhanced superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) levels in the serum of the fatigued rats. The results of this preliminary study indicated that KXS exhibits anti-fatigue activity. This was reflected in the effects on the biochemical markers for fatigue.

Effect of Kaixin-San on depression behavior and hippocampal brain-derived neurotrophic factor in mice

Objective To investigate the effect of Kaixin-San(KXS) on behavior,brain monoamine transmitters,and hippocampal brain-derived neurotrophic factor(BDNF) in mice receiving tail suspension test(TST),so as to explore the correlation of the antidepressant effect of KXS and hippocampal BDNF level.Methods The effect of KXS on the immobility time of mice in the TST was observed.The levels of norepinephrine(NE),dopamine(DA) and 5-hydroxytryptamine(5-HT) in the brain were determined by high-performance liquid chromatography(HPLC).Western blotting analysis was used to examine the expressions of cAMP-response element-binding protein(CREB),p-CREB,and BDNF in the hippocampus.BDNF mRNA expression was also examined by RT-PCR.Pearson's correlation analysis was used to evaluate relationship between anti-depression effect of Kaixin-San and hippocampal BDNF level.Results KXS reduced the immobility time of mice in the TST(P0.05);it also increased the brain levels of monoamine transmitters(DA and 5-HT) and hippocampal levels of CREB,p-CREB and BDNF compared with the control mice(P0.05).Moreover,the anti-depression effect of KXS was correlated with BDNF level (protein:r=-0.694,P0.01;mRNA:r=-0.547,P0.01) in the hippocampus.Conclusion The anti-depression effect of KXS is positively correlated with the hippocampal BDNF level,indicating KXS may exert anti-depression effect via increasing hippocampal BDNF.

Effect of Kai Xin San on Learning and Memory in a Rat Model of Paradoxical Sleep Deprivation

The present study aimed to evaluate the effect of kai xin san (KXS, at doses of 500, 250, and 125 mg/kg body weight per day), a well-known traditional Chinese medicine, on learning and memory in paradoxical sleep deprivation (PSD)-induced cognition deficit rats. Two behavior tests (the Open Field test and the Morris water maze task) were used for testing the effects of KXS on a PSD-induced learning and memory deficit model. Furthermore, its effect on the glutamic acid (GLU) and γ-amino-butyric acid (GABA) levels in the brain tissue, brain-derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB), and phosphorylated-CREB (p-CREB) expression in the hippocampus was also tested. KXS exerted the greatest cognition against the 48 h PSD-induced cognitive deficit and these effects may be mediated by decreasing the GLU and GABA levels and increasing the levels of BDNF, CREB, and p-CREB. This study indicates that the effect of KXS on learning and memory in a rat model of PSD could be associated with the modulation of neurotransmitter levels and the expression of some genes in the brain that contribute to memory functions.

Kai-Xin-San, a Chinese Herbal Decoction Containing Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria, Stimulates the Expression and Secretion of Neurotrophic Factors in Cultured Astrocytes

Kai-xin-san (KXS), a Chinese herbal decoction prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria. In China, KXS has been used to treat stress-related psychiatric diseases with the symptoms of depression and forgetfulness. Although animal study has supported the antidepression function of KXS, the mechanism in cellular level is still unknown. Here, a chemically standardized water extract of KXS was applied onto cultured astrocytes in exploring the action mechanisms of KXS treatment, which significantly stimulated the expression and secretion of neurotrophic factors, including NGF, BDNF, and GDNF, in a dose-dependent manner: the stimulation was both in mRNA and protein levels. In addition, the water extracts of four individual herbs did not significantly stimulate the expression of neurotrophic factors, which could explain the optimized effect of KXS in a herbal decoction. The KXS-induced expression of neurotrophic factors did not depend on signaling mediated by estrogen receptor or protein kinase. The results suggested that the antidepressant-like action of KXS might be mediated by an increase of expression of neurotrophic factors in astrocytes, which fully supported the clinical usage of this decoction.

Effect of Kaixin San on learning and memory in chronic stress depression model rats

To study the effect of classic ancient prescription Kaixin San (KXS) on learning and memory abilities in chronic stress depression model rats and its possible mechanisms. Rats were randomly assigned to six groups: the control group, the model group, the positive drug group (fluoxetine 10 mg x kg(-1)) and KXS groups (1000, 500, 250, 125 mg x kg(-1)). KXS were orally administrated to CMS rats for 21 days. The anti-depression activity of KXS was assessed using the sucrose consumption and the open-field test. The protecting effect for learning and memory abilities was assessed using the Morris water maze (MWM) test. Furthermore, the levels of monoamine neurotransmitters, acetylcholine (Ach) and acetyl cholinesterase (AchE) in the total brain and brain-derived neurotrophic factor (BDNF) protein in the hippocampus were determined. The behavior test showed that KXS significantly increased the sucrose consumption and total distance in the open-field test and notably reduce the incubation period of location and navigation in the MWM test. It could also help increase the number of times passing through the platform, the swimming distance and time in quadrant of original platform, the levels of serotonin (5-HT) and dopamine (DA) , noradrenergic (NE), Ach, BDNF protein and reduce the level of AchE in the CMS-induced rats. KXS can ameliorate the CMS-induced depression behavior in rats and improved their learning and memory abilities, which may be related to the increase in monoamine neurotransmitters, Ach and BDNF levels.

A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats

Kai-xin-san (KXS), a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS-) induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i) the levels of dopamine, norepinephrine, and serotonin (ii) the transcript levels of proteins relating to neurotransmitter metabolism; (iii) the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression.

Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running

Ethnopharmacological relevanceIn traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. Aim of the studyThe present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running. Materials and methodsSeventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13mg/kg/d doge, KXS treatment at 175mg/kg/d, 350mg/kg/d and 700mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA. ResultsCFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment. ConclusionsThe results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS.

The effect of Acorus gramineus on the bioavailabilities and brain concentrations of ginsenosides Rg1, Re and Rb1 after oral administration of Kai-Xin-San preparations in rats

Aim of the study To investigate the effect of Acorus gramineus (AG), a supposed ‘delivering servant’ according to traditional Chinese medicine principles governing multi-herb formula preparation and formulation, on facilitating the uptake of ginsenosides Rg1, Re and Rb1 to the brain after oral administration of Kai-Xin-San (KXS) preparations. Materials and methods Ginseng extracts or KXS with or without AG were administered to rats for pharmacokinetic study and mice for behaviour tests at a dose of 3 g ginseng per kg. The concentrations of ginsenosides in plasma and brain were determined by an LC–MS/MS method, whilst the effects of preparations on spatial learning were evaluated using the Morris water maze test. Results KXS in the presence of AG tended to significantly reverse the learning impairment induced by scopolamine. The presence of AG in the KXS formula led to increases in the initial absorption rate and extent of Rg1 and Re in terms of Cmax1 and AUC 0–3 h compared to KXS without AG. Although KXS were found to increase the bioavailabilities and brain concentrations of ginsenosides relative to ginseng extract, the brain-to-plasma AUC 0–12 h ratios appeared not to be affected. Conclusions The results suggested that the presence of AG in the KXS formula promoted the initial absorption of ginsenosides Rg1 and Re in the gastrointestinal tract, but unlikely affected the brain-to-plasma AUC ratios.

Preventive Action of Kai Xin San Aqueous Extract on Depressive-Like Symptoms and Cognition Deficit Induced by Chronic Mild Stress

Kai Xin San (KXS), a traditional Chinese herbal medicine, has been used clinically for the treatment of depressive disorders and cognitive impairment for centuries. However, the effects of KXS on cognitive dysfunction induced by depression have not been evaluated scientifically. The present study aimed to explore the antidepressant-like and nootropic effects of an aqueous extract of KXS (at doses of 0.3, 0.9, and 2.7 g/kg/day) using chronic mild stress (CMS) as a model of depression. Depressive symptoms were analyzed using the sucrose-preference and novelty-induced inhibition of feeding tests. Cognitive function was evaluated using a two-way active avoidance task. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels, acetylcholinesterase (AChE) protein expression in the hippocampus, and monoamine neurotransmitter concentrations in the prefrontal cortex and hippocampus were also determined to elucidate the neurochemical mechanisms. Experimental results showed that KXS aqueous extract significantly ameliorated the CMS-induced depressive symptoms, including the reduced preference index and prolonged latency to novelty-suppressed feeding. Simultaneously, KXS significantly reversed the CMS-induced decrease in the numbers of active avoidance and active movement distances and increase in the numbers of the passive avoidance and passive movement distances, thereby producing nootropic effects in the two-way active avoidance test. KXS also inhibited the increased AChE expression in the hippocampus, up-regulated the decreased monoamine neurotransmitter concentrations of both brain areas and reduced the elevated ACTH concentrations in the serum induced by CMS. Taken together, these results indicate that KXS exerts its antidepressant-like and nootropic effects in the CMS model by modulating the HPA axis, monoamine neurotransmitter and cholinergic systems.

Behavioral and biochemical effects of Kaixin‐San, a traditional Chinese medicinal empirical formula

AbstractKaixin‐San (KXS), a traditional Chinese medicine, has been used in the treatment of depression. The present study was undertaken to investigate the effects of an ethanolic extract of KXS (KXS‐E) in mouse models of depression, the forced swim test (FST) and tail suspension test (TST). At doses of 500 mg/kg, KXS‐E reduced the immobility time in the FST and TST in mice 30 min after treatment. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC‐ECD. KXS‐E not only increased the concentrations of 5‐HT and NE in whole brain, but also reduced the ratio of 5‐HIAA/5‐HT, slowing down 5‐HT metabolism as compared with mice treated with vehicle+stress. In conclusion, KXS‐E produced antidepressant‐like effects in a mouse model with a mechanism of action that may involve increased 5‐HT and NE in the mouse brain. Drug Dev Res 69:267–271, 2008. © 2008 Wiley‐Liss, Inc.