Efficacy and Safety of a Formulated Herbal Granula, Jiu Wei Zhen Xin, for Generalized Anxiety Disorder: A Meta-Analysis.

BACKGROUND: The traditional Chinese medicine formula Jiu Wei Zhen Xin Granula (JWZXG) is prescribed to treat generalized anxiety disorder (GAD) in China. This study was to assess the efficacy and safety of JWZXG in patients with GAD. METHOD: Data were pooled from 14 randomized controlled trials involving the assessment of mean changes of Hamilton Anxiety Rating Scale (HAMA) total scores, response rates, adverse event rates, quality, publication bias, and risk of bias. RESULTS: Pooled analysis showed no significant difference in response rate (risk ratio 1.01, 95% CI [0.93-1.08]; Z test = 0.17, P = 0.86) and no significant difference between JWZXG group and azapirones group (RR 0.69, 95% CI [0.45, 1.06]; Z test = 1.69, P = 0.09) in rate of adverse events. Though no difference exists between JWZXG group and azapirones group in HAMA total score from baseline, JWZXG group was inferior to selective serotonin reuptake inhibitors (SSRIs) group (WMD -0.93, 95% CI [-1.64, -0.23]; Z test = 2.6, P = 0.009) which had more adverse events than JWZXG group (RR 0.64, 95% CI [0.46, 0.89]; Z test = 2.63, P = 0.009). CONCLUSIONS: This meta-analysis preliminarily suggests that JWZXG is as effective as azapirones, though having the same possibility of suffering AEs. JWZXG was inferior to SSRIs but causes fewer AEs in the treatment of GAD.

Changes in regional cerebral blood flow with Chaihu-Shugan-San in the treatment of major depression.

BACKGROUND: Chaihu-Shugan-San (CHSGS) is a well-known Chinese traditional prescription used for depression. OBJECTIVE: To observe the regional cerebral blood flow (rCBF) changes in patients with major depression and to investigate rCBF and clinical response to CHSGS. MATERIALS AND METHODS: A total of 33 unmedicated patients with major depression and 12 healthy comparison subjects underwent single photon emission computed tomography (SPECT) imaging. A total of 33 unmedicated patients with major depression all met the diagnostic criteria of stagnation of liver qi of traditional Chinese medicine and were divided into two groups: CHSGS group (n = 20) and fluoxetine group (n = 13). SPECT imaging was restudied in posttreatment. RESULTS: SPECT detected abnormalities in all (100.0%) patients both in CHSGS group and fluoxetine group. All healthy subjects were normal results. The depressed patients showed rCBF decreased in the multiple regions. The semiquantitative values of bilateral frontal and left temporal lobes both in CHSGS group and fluoxetine group were lower than that in healthy group (P < 0.05). Reexamined SPECT after 8 weeks treatment with CHSGS showed the consistency between the increase in perfusion defects and the improvement of clinical cerebral symptoms. The semiquantitative values increased in posttreatment, when compared with pretreatment (P < 0.05). CONCLUSION: SPECT represents a sensitive tool to detect the major depressive disorder, which show the rCBF decreased. rCBF perfusion defects can be reversed and clinical symptoms can be improved by CHSGS treatment. CHSGS treatment is effective, well-tolerated, and safe for depression. By semiquantitative analysis, SPECT can objectively detect rCBF changes that is useful for guiding treatment.

Antidepressant-like effects of Chaihu-Shugan-San via SAPK/JNK signal transduction in rat models of depression.

BACKGROUND: Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal herbal formula, registered in Jingyue Quanshu, has been indicated that oral administration of the extract from it can remit depressive disorder. C-Jun amino-terminal kinase (JNK/SAPK) signal transduction plays a key role in the apoptosis of nerve cells, be reported closely correlated with depression. This study was designed to investigate CHSGS antidepressant-like effects in rat models of depression and probe its possible mechanism. MATERIALS AND METHODS: The classical experimental depression model chronic mild unpredictable stress (CMUS) was used to evaluate the antidepressant-like effects of CHSGS. The extracts were administered orally for 14 days, while the parallel positive control was given at the same time using fluoxetine hydrochloride. The expressions of JNK in the hippocampus were detected by real-time fluorescent quantitation PCR and Western blot assay. RESULTS: Intragastric administration of CHSGS for 14 days caused a significant improvement of weight and locomotor activity in the open-field test. In addition, CHSGS treatment inhibited the expressions of JNK in the hippocampus tissue in CMUS rats. CONCLUSION: CHSGS could obviously improve the depressive state of the model rats and its mechanism may be correlated with regulating the expressions of JNK in the hippocampus.

Antidepressant-like activity of Chaihu-Shugan-San aqueous extract in rats and its possible mechanism.

BACKGROUND: Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal formula, is commonly used for the treatment of depression in China. However, the molecular mechanism underlying its antidepressant action is unknown. OBJECTIVE: The objective of this study is to evaluate the antidepressant-like effects of CHSGS and further explore the possible molecular mechanism implicated in its actions. MATERIALS AND METHODS: THE RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: The normal control group, the model control group, the CHSGS group and the fluoxetine control group. The antidepressant-like effects of CHSGS aqueous extract were assessed in rats exposed to chronic mild stress (CMS) using the open-field test and sucrose water consumption test, its underlying mechanism of anti-depression was explored by determining the effect of CHSGS on the extracellular signal-regulated kinase (ERK) and phospho-ERK (P-ERK) in the hippocampus using western blot. The aqueous extract of CHSGS at a dose of standard (5.9 g/kg·d) was administered intragastrically for 14 days during the CMS model while the fluoxetine control group was given at the same time using fluoxetine hydrochloride (1.8 mg/kg·d). RESULTS: The stressed rats demonstrated decreased locomotor activity in open field test and reduction in sucrose consumption and decreased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in the hippocampus. CHSGS alleviated the depressive-like behaviors and increased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in stressed rats as well as fluoxetine. CONCLUSION: In summary, these results suggest that CHSGS aqueous extract possesses an antidepressant-like activity in CMS induced depression model rats, which might be mediated, at least in part, by reversing the stress-induced disruption of ERK activity.

The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS׳s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress. MATERIALS AND METHODS: SD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9 g/kg·d); (2) Component I (3.3 g/kg·d); and (3) Component II (2.6 g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5 ml/kg·d). RESULTS: Depressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats׳ hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured. CONCLUSIONS: CSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS׳s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

OBJECTIVE: To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. METHODS: Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. RESULTS: CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CONCLUSION: CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Meranzin hydrate exhibits anti-depressive and prokinetic-like effects through regulation of the shared α2-adrenoceptor in the brain-gut axis of rats in the forced swimming test.

BACKGROUND: In recent years, the brain-gut axis theory has received increasing attention in studies of depression. However, most studies separately address potential antidepressant and prokinetic treatments. Investigations of drugs that could potentially treat comorbid depression and gastrointestinal (GI) dysfunction via a common mechanism of action have not yet been performed in detail. AIM: To find a common mechanism of action of our patented drug, meranzin hydrate (MH), in the antidepressant and prokinetic treatment. METHODS: The forced swimming test (FST) model of depression, plasma ghrelin measurement, and in vivo and in vitro measurements of GI motility were used. RESULTS: 1. Administration of MH (9 mg/kg) decreased the immobility time during the FST after acute treatment; this effect was inhibited by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-adrenoceptor antagonist, prazosin. 2. After chronic treatment, the immobility time of rats during the FST was decreased significantly by MH (2.25 mg/kg). 3. MH (9 mg/kg) increased plasma ghrelin levels in rats subjected to the FST; this increase was enhanced by the ghrelin receptor agonist, GHRP-6. 4. MH (9 mg/kg) also promoted gastric emptying and intestinal transit in rats with or without FST. 5. In vitro, MH (10 µM) increased jejunal contractions in rats subjected to the FST; this effect was inhibited by yohimbine. Furthermore, the inhibitory effect of yohimbine was partly reversed by the ghrelin receptor agonist, GHRP-6. CONCLUSION: Our study revealed that MH from natural resources exhibits antidepressive and prokinetic-like effects through the regulation of the common mediator, the alpha 2-adrenoceptor.

The involvement of AMPA-ERK1/2-BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate.

It was recently discovered that ketamine can relieve depression in a matter of hours through an action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This is much more rapid than the several weeks required for the available antidepressants to show therapeutic efficacy. However, ketamine has negative side effects. The aim of this study was to determine whether the natural prokinetic drug meranzin hydrate (MH) has a fast-acting antidepressant effect mediated by AMPA receptors. By means of in vivo and in vitro experiments, we found that (1) treatment of rats with MH at 9 mg/kg decreased immobility time in a forced swimming test (FST), as did the popular antidepressant fluoxetine and the AMPA receptor positive modulator aniracetam. Pretreatment of rats with NBQX (10 mg/kg), an antagonist of AMPA receptors, blocked this effect of MH. (2) MH increased number of crossings of forced swimming rats in the open field test. (3) FST enhanced hippocampal ERK1/2, p-ERK1/2 and BDNF expression levels. MH (9 mg/kg) treatment further up-regulated hippocampal p-ERK1/2 and BDNF expression levels, and this effect was prevented by NBQX. (4) MH-increased BDNF expression corresponded with MH-decreased immobility time in the FST. (5) In vitro experiments, we found that incubation of rats hippocampus slices with MH (10, 20 µM respectively) increased concentrations of BDNF and p-ERK1/2. This effect of MH (20 µM) were prevented by NBQX. In conclusion, in animals subjected to acute stress, the natural prokinetic drug MH produced a rapid effect mediated by AMPA receptors and involving BDNF modulation through the ERK1/2 pathway.

Enhanced antitumoral efficacy and immune response following conditionally replicative adenovirus containing constitutive HSF1 delivery to rodent tumors.

BACKGROUND: Oncolytic adenoviruses are promising as anticancer agents but have limited clinical responses. Our previous study showed that heat shock transcription factor 1 (HSF1) overexpression could increase the anti-tumor efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral burst. Due to the important roles of heat shock proteins (HSPs) in eliciting innate and adaptive immunity, we reasoned that besides increasing the viral burst, HSF1 may also play a role in increasing tumor specific immune response. METHODS: In the present study, intra-dermal murine models of melanoma (B16) and colorectal carcinoma (CT26) were treated with E1B55kD deleted oncolytic adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by intra-tumoral injection. Tumors were surgically excised 72 h post injection and animals were analyzed for tumor resistance and survival rate. RESULTS: Approximately 95% of animals in the Adel55-cHSF1 treated group showed sustained resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55, or Adel55-HSF1i treated groups. Only 50-65% animals in the Adel55-HSP70 and Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was associated with development of tumor type specific cellular immune responses. Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment. CONCLUSIONS: Besides by increasing its burst in tumor cells, cHSF1 could also augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the tumor-specific immune response, which is beneficial to prevent tumor recurrence. cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock protein genes.

[Relationship between symptom stratification and syndrome differentiation of traditional Chinese medicine for depressive episode].

On the basis of medical literature review and clinical research experience, the authors analyzed the reasons for low recognition rate of depression and poor progress of traditional Chinese medicine (TCM) differentiation of depression in this paper and put forward that depressive episode symptoms and the corresponding common terminology classification of Chinese and Western medicine should be the breakthrough points. Through symptom stratification and combination, as well as distinguishing between primary and secondary symptoms, the comprehensive integrative medicine clinical assessment of depression was explored so as to further obtain expert consensus and provide a methodology reference for the TCM differentiation of depression and the research of etiology and pathogenesis.

Effect of Chaihu Shugan San and its components on expression of ERK1/2 mRNA in the hippocampus of rats with chronic mild unpredicted stress depression.

OBJECTIVE: To explore the antidepressant effect and mechanism of Chaihu Shugan San (CHSGS) composition, a compound traditional Chinese herb medicine and its components. METHODS: Rats were randomly divided into 6 groups: normal control group, model control group, a CHSGS group, a component I group, a component II group and a fluoxetine control group. The depression model was replicated by chronic unpredictable mild stress and single house for 28 d. Behavioral scores of the rats were detected by Open-field test and sucrose solution consumption test, and ERK1/2 mRNA expression in the hippocampus tissue was assayed by real-time fluorescent quantitative PCR. RESULTS: ERK1/2 mRNA expression was down-regulated in the depression model group compared with the normal control group (P<0.01). Compared with the model group, ERK1/2 mRNA expression in the CHSGS group and fluoxetine group was both up-regulated (P<0.05 or P<0.01); and only ERK1 mRNA expression in the component I group was up-regulated (P<0.05). No significant difference existed between the component II group and the model group (P>0.05). CONCLUSION: Isolated-living condition and chronic mild unpredictable stress can down-regulate the expression of ERK1/2 mRNA in the hippocampus tissue. CHSGS may exert an antidepressant effect through increasing the expression of ERK1/2 mRNA in the hippocampus, component I may play an important role in its antidepression effect, while compatibility of the use of component II can enhance the antidepressant efficacy.

[Effects of Chaihu Shugan San on behavior and plasma levels of corticotropin releasing hormone and adrenocorticotropic hormone of rats with chronic mild unpredicted stress depression].

OBJECTIVE: To investigate the effects of Chaihu Shugan San (CHSGS), a compound traditional Chinese herbal medicine, on behavior and plasma levels of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) of rats with chronic mild unpredicted stress depression. METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups: normal control group, untreated group, fluoxetine group and CHSGS group. Except the normal control group, rats were singly housed and exposed to an unpredicted sequence of mild stressor for continuous 4 weeks to induce depression. Since the fifteenth day, rats were intragastrically administered with equal volume agents respectively for 2 weeks [normal saline for the normal control group and the untreated group, fluoxetine (1.8 mg/kg) for the fluoxetine group and CHSGS (5.9 g/kg) for the CHSGS group]. Behavioral scores of rats were detected by open-field test and sucrose preference test, and the plasma levels of CRH and ACTH in different groups were detected by radioimmunoassay. RESULTS: Compared with the normal control group, body weights of the rats in the untreated group were significantly decreased. Scores of crossing, rears and grooming in open-field test were reduced significantly. Pure water consumption in sucrose preference test was increased significantly. The levels of plasma CRH and ACTH were significantly increased. The depressive behaviors of the rats were improved significantly and the levels of plasma CRH and ACTH were obviously reduced in the CHSGS group. CONCLUSION: Chronic mild unpredicted mild stress can affect the neuroendocrine and behavior and cause depression in rats. CHSGS can regulate HPA hyperactivity of rats caused by chronic stress and has antidepressive effects.

PI-PLC signal pathway: a possible pathogenesis link post-myocardial infarction to depression.

Depressive disorder in the post-myocardial infarction (MI) period has been associated with increased cardiac morbidity and mortality. The most prominent findings are the increased mortality in patients with depression after myocardial infarction. Despite the extensive studies, the possible pathophysiologic mechanisms behind this association have not been clear. More recently, the data have suggested that both depression and post-MI have been associated with an increased activation status of the platelet. And increased sensitivity to platelet activation has been postulated as one of the mechanisms that may underlie increased vulnerability of depressed post-MI patients to cardiac events, suggesting a pathophysiologic cross-talk between the heart and the brain. Considering the similar changes in serotonin(5-HT) and platelet activation through phosphoinositide (PI)-phospholipase C(PLC) pathway, we guess that PI-PLC signal transduction pathway is a common pathogenesis between depression and post-MI, which mediated by 5-HT resulting in the platelet activation. The article introduces the hypothesis that proposes one possibility. This common mechanism of signal pathway may develop other current theories which are beneficial to future therapies to reduce post-MI depression.

[Mechanism and protective effect of glossy ganoderma decoction on the activities of RNA polymerase in hepatocyte of rabbits with Amanita mushroom poisoning].

OBJECTIVE: To investigate the mechanism of glossy ganoderma decoction in Amanita mushroom poisoning. METHODS: Twenty male New Zealand white rabbits were randomly divided into 4 groups, including a normal control, a model poison group, and 2 treatment groups (different doses of glossy ganoderma decoction). The activities of hepatocyte RNA polymerase were measured by ultraviolet spectrophotometry and liver function were measured. RESULTS: The activities of hepatocyte RNA polymerase of the model group significantly decreased, and those of the 2 treatment groups were significantly higher than those of the model group. There was a dose-dependent manner between the 2 treatment groups ( all Ps<0.01), and the differences of liver function test including total bilirubin (TBIL), direct bilirubin (DB), total bile acid (TBA), and alanine aminotransferase (ALT) in the 4 groups were significant (P<0.01). CONCLUSION: Glossy ganoderma decoction may protect the liver from Amanita mushroom poisoning. Its mechanism may be related to the increase of the activities of hepatocyte RNA polymerase.

Study on the interrelationship between 5-HTTLPR/G-protein beta3 subunit (C825T) polymorphisms and depressive disorder.

OBJECTIVE: To assess whether the promoter region of the serotonin transporter gene (5-HTTLPR) and G-protein beta3-subunit (GNbeta3 C825T) polymorphisms are associated with depressive disorder and explore the genetic mechanism concerning the pathogenesis of this disorder. METHODS: The genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Patients suffering from depression (n=184) and sex and age-matched controls (n=158) were compared in this study. RESULTS: The frequencies of 5-HTTLPR SS and GNbeta3 825TT genotypes and 5-HTTLPR S and GNbeta3 825T alleles in patients suffering from depression were significantly higher than those in the controls (P<0.01). Combined genotype analysis showed that individuals with both 5-HTTLPR S and GNbeta3 825T alleles (odds ratio=3.25, P=0.002) had a risk of depressive disorder higher than those with 5-HTTLPR S (odds ratio=1.817, P=0.01) or GNbeta3 825T alleles (odds ratio=2.214, P=0.001) alone. CONCLUSIONS: These results indicated that the etiology of depressive disorder is associated with 5-HTTLPR and GNbeta3 C825T polymorphisms. Our data also suggests that an interaction effect may exist between the 5-HTTLPR S allele and GNbeta3 825T allele in increasing the risk of depressive disorder.

Clinical experience in treatment of Amanita mushroom poisoning with Glossy Ganoderma Decoction and routine Western medicines.

OBJECTIVE: To assess the effects of treatment of Amanita mushroom poisoning with Glossy anoderma Decoction (, GGD). METHODS: Twelve patients with acute Amanita mushroom poisoning received conventional treatment (penicillin and reduced glutathione) combined with oral administration of GGD (treated group), which was prepared out of 200 g Glossy ganoderma decocted in water to 600 mL, and 200 ml was given once, three times a day for 7 successive days; while conventional treatment alone was given to the other 11 patients assigned to the control group. The therapeutic efficacy and changes in serum levels of total bilirubin (TBil), bile acids (BA), alanine transaminase (ALT), and aspartate transaminase (AST) activities in the two groups were compared. RESULTS: The cured-markedly effective rate in the treated group was more significant than that in the control group (P<0.01). Elevation in TBil, BA, ALT, and AST activities were observed in both groups 3 days after poisoning, which progressively increased thereafter in the control group. In the treated group, they reached their peak on the 3rd day and then declined gradually. The differences between pre-treatment and post-treatment in both groups were obviously significant (P<0.01), so were the differences between the two groups at corresponding time points (P<0.01). CONCLUSION: GGD shows excellent clinical efficacy in the treatment of acute Amanita mushroom poisoning and can reduce mortality significantly.

[Anti-depressive effect of Baisong tablets on the chronic mild unpredicted stress depression in rats].

OBJECTIVE: To investigate the effect of Baisong tablets on the nerve-biochemistry and neuroendocrine of chronic mild unpredicted stress depression in rats. METHODS: Sixty male Sprague-Dawley rats were randomly allocated to 4 groups: a normal control (NC), a model control (MC), a fluoxetine control (FC) and a Baisong tablet treatment group (BST). All rats except the control group were singly housed and exposed to an unpredicted sequence of mild stressor. The levels of serotonin (5-HT), glutamate (Glu) and gama-aminobutyric acid (GABA) of the hippocampus were measured by high-performance liquid chromatography. The concentration of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (CORT) in the plasma of the rats were detected by radio-immunity. The CRHmRNA expressions in the hypothalamus and prefrontal cortex were semiquantified by RT-PCR method. The differences of BDNF and TrkB protein expression in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus were investigated with immunohistochemistry technique. RESULTS: In comparison with NC group, the levels of 5-HT, and GABA of the hippocampus in MC rats reduced significantly (P<0.01), and the concentration of CRH, ACTH, and CORT of the plasma and the level of Glu of the hippocampus and CRH mRNA expression in the brain increased significantly. Fluoxetine or Baisong could significantly regulate the abnormal changes of all the above. CONCLUSION: Chronic mild unpredicted stress can affect neuroendoerine and cause depression, and Baisong tablet has antagonism against it.

[Anti-tumor effect and mechanism of Paeonol on the hepatocellular carcinoma cell line Bel-7404].

OBJECTIVE: To investigate the anti-tumor effect of Paeonol (Pae) on the hepatocellular carcinoma cell line Bel-7404 and its molecular mechanisms. METHODS: Hepatocellular carcinoma cell line Bel-7404 was treated by Pae in various concentrations and different time points respectively; and then the cell proliferation was assayed by light microscope, MTT method. DNA agarose gel electrophoresis and TUNEL were used to detect the apoptosis. The expression of PTEN and Akt were examined by RT-PCR and immunocytochemical ABC method. RESULTS: Compared with the control groups Pae obviously increased the inhibitory and apoptosis rate of hepatocellular carcinoma cell line Bel-7404. It also showed a typical apoptotic morphology and DNA depicted a ladder pattern characteristic of the apoptosis, indicating the presence of DNA fragmentation. RT-PCR and immunocytochemical ABC assay showed that Pae could increase the expression of PTEN and decrease the expression of Akt. CONCLUSION: Pae can increase the anti-hepatocellular carcinoma effect, and its mechanism may be the increase of apoptosis-inducing effect which is regulated by phosphatidylinositol-3-kinase.