Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats

Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats

Journal of Ethnopharmacology 128 (2010) 336–341 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevie...

298KB Sizes 2 Downloads 56 Views

Journal of Ethnopharmacology 128 (2010) 336–341

Contents lists available at ScienceDirect

Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm

Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats Qing-Qiu Mao a , Zhen Huang b,∗ , Xiao-Ming Zhong b , Chun-Rong Feng b , Ai-Juan Pan b , Zhao-Yi Li b , Siu-Po Ip a,∗∗ , Chun-Tao Che a a b

School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China College of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou 310053, Zhejiang, China

a r t i c l e

i n f o

Article history: Received 1 November 2009 Received in revised form 18 January 2010 Accepted 25 January 2010 Available online 4 February 2010 Keywords: SYJN Chinese herbal formula Antidepressant Chronic unpredictable stress Behavior BDNF Rat

a b s t r a c t Aim of the study: Suyu-Jiaonang (SYJN) is a Chinese herbal formula that contains four herbs: Bupleurum chinense DC, Curcuma aromatica Salisb., Perilla frutescens (Linn.) Britt., and Acorus tatarinowii Schott. Previous studies conducted in our laboratory have revealed an antidepressant-like effect of the formula in various mouse models of behavioral despair. The present study aimed to investigate whether SYJN could produce antidepressant-like effects in chronic unpredictable stress (CUS)-induced depression model in rats and its possible mechanism(s). Materials and methods: Rats were subjected to an experimental setting of CUS. The effect of SYJN treatment on CUS-induced depression was examined using behavioral tests including the sucrose consumption and open field tests. The mechanism underlying the antidepressant-like action of SYJN was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats. Results: Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption and locomotor activity (assessed in the open field test). In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily intragastric administration of SYJN (1300 or 2600 mg/kg) during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUSinduced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex. Conclusion: The results suggest that SYJN alleviates depression induced by CUS. The antidepressant-like activity of SYJN is likely mediated by the increase in BDNF expression in brain tissues. © 2010 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Depression is a commonly occurring, debilitating, and lifethreatening psychiatric disorder characterized by a pervasive low mood, loss of interest or pleasure in daily activities, low selfesteem, and suicidal tendencies (Hankin, 2006; Perahia et al., 2009). According to the World Health Organization, depression is expected to become the second leading cause of disease-related disability by the year 2020 (Rybnikova et al., 2007). Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family (Murakami et al., 2005). Postmortem analyses have revealed lower levels of BDNF in patients with major depression (Castrén et al., 2007), while BDNF infusion into the brain has been found

∗ Corresponding author. Tel.: +86 571 86613576; fax: +86 571 87049157. ∗∗ Corresponding author. Tel.: +852 31634457; fax: +852 31634459. E-mail addresses: [email protected] (Z. Huang), [email protected] (S.-P. Ip). 0378-8741/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2010.01.050

to produce antidepressant-like action (Siuciak et al., 1997). Clinical studies have found decreased BDNF levels in the blood of depressive patients (Karege et al., 2002, 2005; Aydemir et al., 2006, 2007), while antidepressant treatment seems to be able to normalize BDNF levels (Shimizu et al., 2003; Bas¸terzi et al., 2009). BDNF is thus an attractive topic in research into the pathophysiology of depression and the mechanism of action of antidepressants. Synthetic antidepressant drugs are widely available on the pharmaceutical market (Bouvier et al., 2003). However, because of the involvement of multiple pathogenic factors in depression, many of these drugs have a low response rate, and some even cause adverse side effects (Park et al., 2007). Therefore, the search continues for a safer, better tolerated, and powerful antidepressant drug. Traditional Chinese medicine includes many herbal formulae with psychotropic potential. One of them, Suyu-Jiaonang (SYJN), is composed of four herbs: Bupleurum chinense DC, Curcuma aromatica Salisb., Perilla frutescens (Linn.) Britt., and Acorus tatarinowii Schott (in a ratio of 4:3:4:3). SYJN has been successfully used to treat depression-like disorders in the clinical practice

Q.-Q. Mao et al. / Journal of Ethnopharmacology 128 (2010) 336–341

of Chinese herbal medicine. Previous pharmacological studies in our laboratory demonstrated that intragastric administration of SYJN significantly decreased immobility time in the tail suspension and forced swim tests in mice (Zhong et al., 2006a). The herbal preparation was also effective in improving chronic stress-induced behavioral alterations in mice, which were related to monoaminergic neurotransmitter systems (Zhong et al., 2006a,b). However, no studies to date have investigated the molecular targets of SYJN relevant to its antidepressant effects. In this study, the antidepressant-like effect of SYJN treatment (650, 1300, and 2600 mg/kg, intragastrically) was evaluated in a rat model of depression induced by chronic unpredictable stress (CUS). The molecular mechanism underlying the antidepressantlike action of SYJN was investigated by measuring BDNF protein and mRNA levels in brain tissues of CUS-exposed rats. 2. Materials and methods 2.1. Preparation of SYJN All the crude drugs of SYJN were purchased from Zhejiang Provincial Hospital of Traditional Chinese Medicine (Zhejiang Province, China) and identified by Professor K.R. Chen. The herbal materials were extracted as previously described (Huang et al., 2009). Briefly, Bupleurum chinense DC, Curcuma aromatica Salisb., Perilla frutescens (Linn.) Britt., and Acorus tatarinowii Schott were mixed at a ratio of 4:3:4:3, which was adopted from the clinical practice of Chinese herbal medicine. The mixture was left to macerate in distilled water (1:8, w/v) for 30 min at room temperature with occasional stirring, and then boiled for 60 min. This extraction method is identical to that used in clinical settings. Next, the cooled extract was filtered. The extraction procedure was repeated twice. The extracted fractions were pooled and concentrated using a rotary evaporator. The remaining water was removed by freeze drying, and the final yield of SYJN extract was 19% (w/w). 2.2. Drugs Imipramine hydrochloride, a tricyclic antidepressant, was purchased from Sigma–Aldrich (St. Louis, MO) and used as positive control for antidepressant action. All other reagents and solvents were of analytical grade.

337

intragastrically 30 min before each stressor once every day for 4 weeks as previously described (An et al., 2008a,b). In the clinical practice of Chinese herbal medicine, SYJN is usually prescribed at a daily dose of 42 g of herbal materials. When this human dose was converted into an animal dose (at an extraction yield of 19%, a person of 60 kg, and a conversion factor of 10 between human and rat), it was equivalent to the middle dose (1.3 g extract/kg) used in this study. SYJN and imipramine were dissolved in physiological saline, and the animals in the control and CUS plus vehicle groups were treated with equal amounts of physiological saline (10 ml/kg). The CUS procedure was performed as described by Mao et al. (2009), with a slight modification. Briefly, CUS consisted of a variety of unpredictable stressors, including 48-h food deprivation, 24-h water deprivation, 5-min cold water swim (at 4 ◦ C), 1-min tail pinch (1 cm from the end of the tail), foot shock (1 mA, 1-s duration, average 1 shock/min) for 60 min, exposure to a foreign object (e.g., a piece of plastic) for 24 h, and overnight illumination. One of these stressors (in random order) was given every day between 9:00 a.m. and 12:00 a.m. for 4 weeks. Control (unstressed) animals were undisturbed except for necessary procedures such as routine cage cleaning. 2.5. Sucrose preference test The sucrose preference test was carried out at the beginning and the end of 4-week period of CUS exposure. The test was performed as described previously (Luo et al., 2008), with minor modifications. Briefly, before the test, the rats were trained to adapt to sucrose solution (1%, w/v): two bottles of sucrose solution were placed in each cage for 24 h, and then one bottle of sucrose solution was replaced with water for 24 h. After the adaptation procedure, the rats were deprived of water and food for 24 h. The sucrose preference test was conducted at 9:00 a.m. The rats were housed in individual cages and given free access to two bottles containing 100 ml of sucrose solution (1%, w/v) and 100 ml of water, respectively. After 60 min, the volume of both the consumed sucrose solution and water was recorded, and sucrose preference was calculated using the following formula: Sucrose preference =

sucrose consumption water consumption + sucrose consumption ×100%.

2.3. Animals 2.6. Open field test Male Sprague–Dawley rats weighing 180–220 g were obtained from the Laboratory Animal Services Center, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang. The animals were maintained on a 12-h light/dark cycle (lights on at 6:00 a.m., lights off at 6:00 p.m.) under controlled temperature conditions (22 ± 2 ◦ C), and given standard food and water ad libitum. They were allowed to acclimatize for 7 days before use. All experiments conformed to the guidelines of the “Principles of Laboratory Animal Care” (NIH publication No. 80-23, revised 1996) and the legislation of the People’s Republic of China for the use and care of laboratory animals. The experimental protocols were approved by the Animal Experimentation Ethics Committee of the Chinese University of Hong Kong. Effort was made to minimize the number and suffering of the animals.

The open field test was carried out at the beginning and the end of 4-week period of CUS exposure. The test was modified from previously described methods (Mao et al., 2008; Zhao et al., 2008). Briefly, the open field apparatus consisted of a square wooden arena (100 cm × 100 cm × 50 cm) with a black surface covering the inside walls. The floor of the wooden arena was divided equally into 25 squares marked by black lines. In the test, a single rat was placed in the center of the arena and allowed to explore freely. The number of crossings (squares crossed with all paws) and rearings (raising of the front paws) were recorded during a test period of 5 min. This apparatus was cleaned with a detergent and dried after occupancy by each rat. 2.7. Tissue sample collection

2.4. Chronic unpredictable stress (CUS) procedure The rats were randomly assigned to six groups of eight individuals: control, CUS plus vehicle, CUS plus SYJN (650 mg/kg), CUS plus SYJN (1300 mg/kg), CUS plus SYJN (2600 mg/kg), and CUS plus imipramine (20 mg/kg). SYJN and imipramine were each given

Twenty-four hours after the completion of the last behavioral test, the rats were sacrificed by decapitation. The whole brain of each rat was rapidly removed and chilled in an ice-cold saline solution. Various brain areas, including the hippocampus and frontal cortex, were dissected on a cold plate and immediately frozen in

338

Q.-Q. Mao et al. / Journal of Ethnopharmacology 128 (2010) 336–341

liquid nitrogen. The tissue samples were stored at −80 ◦ C until assay. 2.8. Measurement of BDNF protein levels in the hippocampus and frontal cortex The content of BDNF protein was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Chemicon International, Temecula, CA) according to the manufacturer’s instructions. The hippocampus and frontal cortex samples were weighed and homogenized in 10-fold volume of lysis buffer. The homogenate was centrifuged at 14,000 × g for 30 min at 4 ◦ C, and the supernatants were collected and stored at −80 ◦ C until assay. All samples and standards were applied in duplicate into 96-well immunoplates precoated with rabbit anti-human BDNF antibody, which were incubated on a shaker overnight at 4 ◦ C. After washing four times, biotinylated mouse anti-BDNF antibody was added and the immunoplates were incubated for 3 h at room temperature. After washing, streptavidin-HRP conjugate solution was added and the immunoplates were incubated at room temperature for 1 h. TMB/E substrate was added and the immunoplates were incubated at room temperature for 15 min. The plates were immediately read by a microplate reader at 450 nm. The detection limit of the assay is ∼7.8 pg/ml. 2.9. Measurement of BDNF mRNA levels in the hippocampus and frontal cortex Total RNA from the hippocampus and frontal cortex was isolated with TRIzol® Reagent (Gibco, Grand Island, NY) according to the manufacturer’s protocol. Concentrations of extracted RNA were calculated from the absorbance at 260 nm. The quality of RNA was assessed by absorbances at 260 and 280 nm, with a ratio of A260 to A280 ranging from 1.9 to 2.1 considered acceptable. Total RNA (1.5 ␮g) was transcribed using a high capacity cDNA reverse transcription kit (Applied Biosystems, Inc., Foster City, CA) according to the manufacturer’s protocol. Assays-on-demand primers for BDNF (Rn02531967 s1) and ␤-actin (Rn00667869 m1) were purchased from Applied Biosystems, Inc. (Foster City, CA). Real-time quantitative polymerase chain reaction (PCR) analysis was performed with a TaqMan® Fast Universal PCR Master Mix Kit (Applied Biosystems, Inc., Foster City, CA) using the StepOnePlusTM real-time PCR system (Applied Biosystems, Inc., Foster City, CA) with the following profile: 2 min hold at 50 ◦ C, 10 min hold at 95 ◦ C, followed by 40 cycles of 15 s at 95 ◦ C and 1 min at 60 ◦ C. Sequence Detection System Software (Version 1.0, Applied Biosystems, Inc., Foster City, CA) was used for data analysis. The relative expression of BDNF mRNA was normalized to the amount of ␤-actin in the same cDNA using the relative quantification method (2−CT method) described by the manufacturer.

Fig. 1. Effect of SYJN treatment on the percentage of sucrose consumption in CUSexposed rats. Values given are the mean ± SEM (n = 8). # p < 0.01 as compared with the control group; *p < 0.05 and **p < 0.01 as compared with the vehicle-treated CUS group.

of sucrose consumption among all rats (data not shown). A 4week period of CUS exposure resulted in a significant reduction in the percentage of sucrose consumption in the animals (37%), as compared to the controls (i.e., non-CUS-exposed rats). Long-term treatment with SYJN at daily doses of 1300 or 2600 mg/kg resulted in significant increases in the percentage of sucrose consumption in CUS-exposed rats (27 and 38%, respectively), as compared to the vehicle-treated and CUS-exposed rats (i.e., vehicle controls). Treatment with imipramine (20 mg/kg), a positive control, also significantly increased the percentage of sucrose consumption in CUS-exposed rats (43%). 3.2. Effect of SYJN on locomotor activity in the open field test Fig. 2 shows the effect of SYJN treatment on locomotor activity in CUS-exposed rats. Locomotor activity was assessed by the number of crossings and rearings in the open field test. Before CUS treatment was given, there was no significant difference in the number of crossings and rearings among all rats (data not shown). A 4-week period of CUS exposure resulted in a significant reduction in the

2.10. Statistical analysis Data were expressed as the mean ± SEM. Multiple group comparisons were performed using one-way analysis of variance (ANOVA) followed by Dunnett’s test to detect intergroup differences. A difference was considered statistically significant when the p value was less than 0.05. 3. Results 3.1. Effect of SYJN on the percentage of sucrose consumption Fig. 1 shows the effect of SYJN treatment on the percentage of sucrose consumption in CUS-exposed rats. Before CUS treatment was given, there was no significant difference in the percentage

Fig. 2. Effect of SYJN treatment on the number of crossings (A) and rearings (B) in the open field test in CUS-exposed rats. Values given are the mean ± SEM (n = 8). # p < 0.01 as compared with the control group; *p < 0.05 and **p < 0.01 as compared with the vehicle-treated CUS group.

Q.-Q. Mao et al. / Journal of Ethnopharmacology 128 (2010) 336–341

339

Fig. 3. Effect of SYJN treatment on brain-derived neurotrophin factor (BDNF) protein levels in the hippocampus (A) and frontal cortex (B) of CUS-exposed rats. Values given are the mean ± SEM (n = 6). # p < 0.01 as compared with the control group; *p < 0.05 and **p < 0.01 compared with the vehicle-treated CUS group.

Fig. 4. Effect of SYJN treatment on brain-derived neurotrophin factor (BDNF) mRNA levels in the hippocampus (A) and frontal cortex (B) of CUS-exposed rats. Values given are the mean ± SEM (n = 6). # p < 0.01 as compared with the control group; *p < 0.05 and **p < 0.01 as compared with the vehicle-treated CUS group.

number of crossings (Fig. 2A) and rearings (Fig. 2B) in rats (60 and 67%, respectively), as compared to the controls. Long-term treatment with SYJN at daily doses of 1300 or 2600 mg/kg significantly increased the number of crossings and rearings in CUS-exposed rats (55 and 74%, respectively), as compared to the vehicle controls. Long-term treatment with SYJN at daily dose of 2600 mg/kg also significantly increased the number of rearings in CUS-exposed rats (87%), as compared to the vehicle controls. Treatment with imipramine (20 mg/kg) also significantly increased the number of crossings and rearings in CUS-exposed rats (92 and 96%, respectively).

of 1300 or 2600 mg/kg significantly increased BDNF mRNA levels in both the hippocampus (45 and 81%, respectively) and frontal cortex (49 and 102%, respectively) of CUS-exposed rats, as compared to the vehicle controls. Imipramine treatment (20 mg/kg) also significantly increased BDNF protein levels in both the hippocampus and frontal cortex of CUS-exposed rats (83 and 106%, respectively).

3.3. Effect of SYJN on BDNF protein levels in the hippocampus and frontal cortex Fig. 3 shows the effect of SYJN treatment on BDNF protein levels in the hippocampus and frontal cortex of CUS-exposed rats. CUS significantly decreased BDNF protein levels in the hippocampus (Fig. 3A) and frontal cortex (Fig. 3B) of rats (49 and 63%, respectively), as compared to the controls. SYJN treatment at daily doses of 1300 or 2600 mg/kg significantly increased BDNF protein levels in both the hippocampus (32 and 83%, respectively) and frontal cortex (80 and 104%, respectively) of CUS-exposed rats, as compared to the vehicle controls. Imipramine treatment (20 mg/kg) also significantly increased BDNF protein levels in both the hippocampus and frontal cortex of CUS-exposed rats (88 and 118%, respectively). 3.4. Effect of SYJN on BDNF mRNA levels in the hippocampus and frontal cortex Fig. 4 shows the effect of SYJN treatment on BDNF mRNA levels in the hippocampus and frontal cortex of CUS-exposed rats. CUS significantly decreased BDNF mRNA levels in the hippocampus (Fig. 4A) and frontal cortex (Fig. 4B) of rats (49 and 59%, respectively), as compared to the controls. SYJN treatment at daily doses

4. Discussion In the present study, we investigated the effects of SYJN, a Chinese herbal formula, on rats exposed to CUS, using the sucrose preference and open field tests to assess their behavior, and measuring BDNF protein and mRNA levels in the hippocampus and frontal cortex. The results demonstrated that SYJN treatment at a daily dose of 1300 or 2600 mg/kg not only had a potent antidepressant-like effect on CUS-induced depression model in rats but also attenuated the decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex of CUS-exposed rats. CUS-induced depression has been widely used for investigating the pathophysiology of depression and associated therapeutic interventions (Katz et al., 1981; Willner, 1997, 2005). Several studies suggest that CUS can induce long-term behavioral disturbances that resemble the symptoms of clinical depression (Katz et al., 1981; Willner, 1997, 2005; Luo et al., 2008), and that CUS-induced depression animal models can be used for evaluating the efficacy of antidepressant candidates through behavioral tests including the sucrose preference and open field tests (Katz et al., 1981; Willner, 1997; Li et al., 2007; Zhao et al., 2008). The sucrose preference test is an indicator of anhedonia-like behavioral change (Willner, 1997, 2005). Anhedonia, a core symptom of major depression among humans, is modeled by inducing a decrease in responsiveness to rewards reflected by reduced consumption of and/or preference for sweetened solutions (Willner, 1997, 2005). The results of the present study show that rats subjected to a 4-week period of CUS consumed less sucrose solution compared to non-stressed

340

Q.-Q. Mao et al. / Journal of Ethnopharmacology 128 (2010) 336–341

rats. Long-term treatment with SYJN significantly suppressed this behavioral change, which indicates the antidepressant-like action of the herbal preparation. In the open field test, normal animals usually show increased locomotor activity in a novel open field, which is driven by the instinct for exploration in a new environment (Luo et al., 2008). However, after chronic stress, animals display decreased locomotor activity in a novel open field (Katz et al., 1981; D’Aquila et al., 2000), which is indicative of a behavioral change that may reflect certain aspects of refractory depression, or loss of interest (Katz et al., 1981; Luo et al., 2008). In the present study, we found that exposure to CUS for a period of 4 weeks led to a significant reduction in the number of crossings and rearings in the open field test among the CUS-exposed rats. However, the CUS-induced decrease in locomotor activity was ameliorated by long-term SYJN treatment during the course of CUS. Recent clinical studies of depression have paid special attention to the hippocampus and frontal cortex, which are brain regions structurally and functionally affected by stress responses and critically involved in the regulation of mood and learning/memory function (Luo et al., 2008; Qi et al., 2008). A causal relationship has been found between the incidence of major depressive disorders and neuronal atrophy/destruction in the hippocampus and frontal cortex (Manji and Duman, 2001; Fuchs et al., 2004). BDNF, which modulates neuronal plasticity, inhibits cell death cascades and increases the cell survival proteins that are responsible for the proliferation and maintenance of central nervous system neurons (Aydemir et al., 2006; Yulu˘g et al., 2009); hence, it may be an important factor in the development and treatment of depression. In experimental studies, it has been found that a decrease in BDNF expression in the hippocampus and frontal cortex among animals exposed to chronic stress can be reversed by antidepressant treatment (Xu et al., 2006; Li et al., 2007). Monteggia et al. (2007) showed that conditional BDNF knockout mice displayed an increase in depression-like behavior, which was assessed by the forced swim and sucrose preference tests. Ibarguen-Vargas et al. (2009) demonstrated that BDNF deficit can dampen the effects of antidepressants in mice exposed to chronic unpredictable mild stress. These studies provide evidence of the role of BDNF in depression, and indicate that the up-regulation of BDNF expression may contribute to the action of antidepressants (Song et al., 2006). Consistent with this view, the present study shows that CUS exposure decreases BDNF protein and mRNA levels in both the hippocampus and frontal cortex of rats, while long-term treatment SYJN for the period of CUS exposure significantly reverses the CUS-induced changes in BDNF protein and mRNA levels. Several studies have shown that increased levels of monoaminergic neurotransmitters including noradrenaline (NA), serotonin (5-HT), and dopamine (DA) induce BDNF expression in the hippocampus and cerebral cortex (Fawcett et al., 1998; Ivy et al., 2003; Juric et al., 2006). NA, 5-HT, and DA have also been found to be able to potently and transiently increase BDNF cellular content in rat neonatal astrocytes in vitro (Miklic et al., 2004; Juric et al., 2006). In addition, the activation of 5-HT receptors coupled to cAMP production and CREB activation can induce BDNF gene transcription (Mattson et al., 2004). The foregoing findings suggest the involvement of monoaminergic systems in the regulation of BDNF production (Juric et al., 2006). The present results, which show that imipramine significantly increased BDNF expression in the hippocampus and frontal cortex of CUS-treated rats, confirm this hypothesis. In previous studies, we demonstrated that SYJN can significantly increase the content of NA, 5-HT, and DA in chronic stress-treated mice (Zhong et al., 2006a), which suggests that a positive correlation exists between BDNF expression and monoaminergic neurotransmitters induced by SYJN treatment. In conclusion, long-term treatment with SYJN was found to alleviate CUS-induced depression. The molecular mechanism

underlying the antidepressant action of SYJN may be mediated by the increase in BDNF expression in brain tissues. Acknowledgements This study was supported by funding from the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (awarded to Professor Huang Zhen) and the Ministry of Health Science Foundation—Grand Science and Technology Project of Medicine and Hygiene of Zhejiang Province (grant no. WKJ20072-020). References An, L., Zhang, Y.Z., Yu, N.J., Liu, X.M., Zhao, N., Yuan, L., Chen, H.X., Li, Y.F., 2008a. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 1484–1490. An, L., Zhang, Y.Z., Yu, N.J., Liu, X.M., Zhao, N., Yuan, L., Li, Y.F., 2008b. Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang. Pharmacology Biochemistry and Behavior 89, 572–580. Aydemir, C., Yalcin, E.S., Aksaray, S., Kisa, C., Yildirim, S.G., Uzbay, T., Goka, E., 2006. Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Progress in Neuro-Psychopharmacology and Biological Psychiatry 30, 1256–1260. Aydemir, O., Deveci, A., Taskin, O.E., Taneli, F., Esen-Danaci, A., 2007. Serum brainderived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 1023–1026. Bas¸terzi, A.D., Yazici, K., Aslan, E., Delialio˘glu, N., Tas¸delen, B., Acar, S.T., Yazici, A., 2009. Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 33, 281–285. Bouvier, N., Trenque, T., Millart, H., 2003. Development of antidepressant drugs. Experience and prospects. Presse Medicale 32, 519–522. Castrén, E., Võikar, V., Rantamäki, T., 2007. Role of neurotrophic factors in depression. Current Opinion in Pharmacology l7, 18–21. D’Aquila, P.S., Peana, A.T., Carboni, V., Serra, G., 2000. Exploratory behaviour and grooming after repeated restraint and chronic mild stress: effect of desipramine. European Journal of Pharmacology 399, 43–47. Fawcett, J.P., Bamji, S.X., Causing, C.G., Aloyz, R., Ase, A.R., Reader, T.A., McLean, J.H., Miller, F.D., 1998. Functional evidence that BDNF is an anterograde neuronal trophic factor in the CNS. Journal of Neuroscience 18, 2808–2821. Fuchs, E., Czeh, B., Kole, M.H., Michaelis, T., Lucassen, P.J., 2004. Alterations of neuroplasticity in depression: the hippocampus and beyond. European Neuropsychopharmacology 5, S481–S490. Hankin, B.L., 2006. Adolescent depression: description, causes, and interventions. Epilepsy & Behavior 8, 102–114. Huang, Z., Mao, Q.Q., Zhong, X.M., Feng, C.R., Pan, A.J., Li, Z.Y., 2009. Herbal formula SYJN protect PC12 cells from neurotoxicity induced by corticosterone. Journal of Ethnopharmacology 125, 456–460. Ibarguen-Vargas, Y., Surget, A., Vourc’h, P., Leman, S., Andres, C.R., Gardier, A.M., Belzung, C., 2009. Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress. Behavioural Brain Research 202, 245–251. Ivy, A.S., Rodriguez, F.G., Garcia, C., Chen, M.J., Russo-Neustadt, A.A., 2003. Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacology Biochemistry and Behavior 75, 81–88. Juric, D.M., Miklic, S., Carman-Krzan, M., 2006. Monoaminergic neuronal activity up-regulates BDNF synthesis in cultured neonatal rat astrocytes. Brain Research 1108, 54–62. Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., Aubry, J.M., 2002. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research 109, 143–148. Karege, F., Bondolfi, G., Gervasoni, N., Schwald, M., Aubry, J.M., Bertschy, G., 2005. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biological Psychiatry 57, 1068–1072. Katz, R.J., Roth, K.A., Schmaltz, K., 1981. Amphetamine and tranylcypromine in an animal model of depression: pharmacological specificity of the reversal effect. Neuroscience and Biobehavioral Reviews 5, 259–264. Li, S., Wang, C., Wang, M., Li, W., Matsumoto, K., Tang, Y., 2007. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sciences 15, 1373–1381. Luo, D.D., An, S.C., Zhang, X., 2008. Involvement of hippocampal serotonin and neuropeptide Y in depression induced by chronic unpredicted mild stress. Brain Research Bulletin 77, 8–12. Manji, H.K., Duman, R.S., 2001. Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacology Bulletin 35, 45–49.

Q.-Q. Mao et al. / Journal of Ethnopharmacology 128 (2010) 336–341 Mao, Q.Q., Ip, S.P., Tsai, S.H., Che, C.T., 2008. Antidepressant-like effect of peony glycosides in mice. Journal of Ethnopharmacology 119, 272–275. Mao, Q.Q., Ip, S.P., Ko, K.M., Tsai, S.H., Xian, Y.F., Che, C.T., 2009. Effects of peony glycosides on mice exposed to chronic unpredictable stress: further evidence for antidepressant-like activity. Journal of Ethnopharmacology 124, 316–320. Mattson, M.P., Maudsley, S., Martin, B., 2004. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends in Neurosciences 27, 589–594. Miklic, S., Juric, D.M., Carman-Krzan, M., 2004. Differences in the regulation of BDNF and NGF synthesis in cultured neonatal rat astrocytes. International Journal of Developmental Neuroscience 22, 119–130. Monteggia, L.M., Luikart, B., Barrot, M., Theobold, D., Malkovska, I., Nef, S., Parada, L.F., Nestler, E.J., 2007. Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biological Psychiatry 61, 187–197. Murakami, S., Imbe, H., Morikawa, Y., Kubo, C., Senba, E., 2005. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neuroscience Research 53, 129–139. Park, S.W., Kim, Y.K., Lee, J.G., Kim, S.H., Kim, J.M., Yoon, J.S., Park, Y.K., Lee, Y.K., Kim, Y.H., 2007. Antidepressant-like effects of the traditional Chinese medicine kami-shoyo-san in rats. Psychiatry and Clinical Neurosciences 61, 401–406. Perahia, D.G., Quail, D., Desaiah, D., Montejo, A.L., Schatzberg, A.F., 2009. Switching to duloxetine in selective serotonin reuptake inhibitor non- and partialresponders: effects on painful physical symptoms of depression. Journal of Psychiatric Research 43, 512–518. Qi, X., Lin, W., Li, J., Li, H., Wang, W., Wang, D., Sun, M., 2008. Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiology of Disease 31, 278–285. Rybnikova, E., Mironova, V., Pivina, S., Tulkova, E., Ordyan, N., Vataeva, L., Vershinina, E., Abritalin, E., Kolchev, A., Nalivaeva, N., Turner, A.J., Samoilov, M., 2007.

341

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats. Neuroscience Letters 417, 234–239. Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., Nakazato, M., Watanabe, H., Shinoda, N., Okada, S., Iyo, M., 2003. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry 54, 70–75. Siuciak, J.A., Lewis, D.R., Wiegand, S.J., Lindsay, R.M., 1997. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacology Biochemistry and Behavior 56, 131–137. Song, L., Che, W., Min-Wei, W., Murakami, Y., Matsumoto, K., 2006. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress. Pharmacology Biochemistry and Behavior 83, 186–193. Willner, P., 1997. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134, 319–329. Willner, P., 2005. Chronic mild stress (CMS) revisited: consistency and behaviouralneurobiological concordance in the effects of CMS. Neuropsychobiology 52, 90–110. Xu, Y., Ku, B., Tie, L., Yao, H., Jiang, W., Ma, X., Li, X., 2006. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Research 1122, 56–64. Yulu˘g, B., Ozan, E., Gönül, A.S., Kilic, E., 2009. Brain-derived neurotrophic factor, stress and depression: a minireview. Brain Research Bulletin 78, 267–269. Zhao, Z., Wang, W., Guo, H., Zhou, D., 2008. Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis in chronic variable stress induced depression model rats. Behavioural Brain Research 194, 108–113. Zhong, X.M., Mao, Q.Q., Huang, Z., Wei, J.P., 2006a. Effect of Suyu capsule in depression model mice. Chinese Journal of New Drugs 15, 1247–1250. Zhong, X.M., Mao, Q.Q., Huang, Z., Wei, J.P., Liang, Z.H., 2006b. The effect of Suyu capsule on behavior and injury of hippocampal neurons in the depression model mice. China Journal of Chinese Materia Medica 31, 1192–1195.