Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus / 中西医结合学报

OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Application of nerve trunk stimulation therapy in functional rehabilitation of the lower limbs in the patients with cerebral apoplexy at convalescence stage / 针刺研究

OBJECTIVE: To explore the value of nerve trunk stimulation in the rehabilitation of lower limb function in the patients with cerebral apoplexy at convalescence stage. METHODS: According the random number table, the patients with the lower limb dysfunction of cerebral apoplexy at convalescence stage were divided into a control group and a treatment group, 42 cases in each group. The drug therapy and the routine rehabilitation training were provided in the two groups. Additionally, in the treatment group, the nerve trunk stimulation therapy was adopted， in which, Chize (LU5，stimulating point of radial nerve), Neiguan (PC6, stimulating point of median nerve), Xiaohai (SI8, stimulating point of ulnar nerve) were selected. In the control group, acupuncture intervention was supplemented. Before and after treatment, the peak torque (PT) of the lower flexor-extensor muscle of the knee joint, gait parameters，the score of the modified Ashworth spasm scale (MAS), the score of Fugl-Meyer motor assessment (FMA) and the score of Fugl-Meyer balance scale (FBS) were recorded. RESULTS: After the treatment, the PT of the lower flexor-extensor muscle of the knee joint，the scores of FMA and FBS，the step speed and frequency were all increased, the score of MAS and the difference in the stride between the left and the right were decreased as compared with those before treatment (P<0.01). After the treatment, The PT of the lower flexor-extensor muscle of the knee joint，the scores of FMA and FBS，the step speed and frequency in the treatment group were higher than those in the control group (P<0.01). The score of MAS and the difference in the stride between the left and the right in the treatment group were lower than those in the control group (P<0.01). CONCLUSION: Nerve trunk stimulation therapy quite effectively increases the muscle strength and relieves the muscle tension as well as improves the motor function, the balance and the walking pattern of the lower limbs. This therapy is significantly valuable in the rehabilitation of the lower limbs in the patients with cerebral apoplexy at convalescence stage.

Development and evaluation of Chinese medicine fire-heat syndrome scale in oral cavity for measuring Chinese herb toothpaste / 中国结合医学杂志

<p><b>OBJECTIVE</b>To formulate the standard measuring tool for the evaluations on fire-heat syndrome in oral cavity by means of Chinese medicine (CM).</p><p><b>METHODS</b>The measuring scale for fire-heat syndrome in the oral cavity by means of CM was investigated by symptom collection, item pool formulation, item selection, pre-investigation, evaluations on the reliability, validity and reactivity of the measuring scale, according to the principles for measuring scale design and under the guidance of CM theories.</p><p><b>RESULTS</b>The measuring scale was composed of two integrative parts: the self-filling section and the interview section. As far as the reliability was concerned, the total Cronbach α coefficient of the measuring scale was 0.866, the total test-retest reliability coefficient was 0.726 and the split-half reliability coefficient was 0.851. As far as the validity was concerned, the scores for the subjects of fire-heat syndrome in oral cavity and healthy people in their oral cavity in the items of symptoms were statistically different (P<0.01); three common divisors were extracted according to the theoretical dimensions, the accumulated contribution rate was 63.468%. As far as the reactivity was concerned, the difference between the symptom scores before and after the test in which 31 subjects used the Chinese herb toothpaste was statistically significant (P<0.01).</p><p><b>CONCLUSIONS</b>This measuring scale has relatively good reliability, validity and reactivity, and it can be used in an objective quantitative evaluation on patients suffering from fire-heat syndrome in oral cavity, and thus lay the foundations for the evaluations on the therapeutic effects of Chinese herb toothpaste on fire-heat syndrome in oral cavity.</p>

Comparative study on effects of Xiaoyao Powder and its modified prescription on plasma metabolomics of rats with chronic immobilization stress / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the changes in the levels of endogenous metabolites in rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its modified prescription version, which lacks the volatile oils extracted from Herba Menthae.</p><p><b>METHODS</b>Twenty-four experimental male SD rats were randomly divided into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control group rats were subjected to CIS 3 h per day for 21 consecutive days. Groups XYP-1 and XYP-2 were given the extracted XYS with or without volatile oils (3.854 g/kg; suspended in distilled water) via gavage 1 h before CIS each day for 21 days. Rats were anesthetized using intraperitoneal injection of pentobarbital sodium (40 mg/kg) on the 22nd day. Observations were made using a Varian INOVA 600 MHz NMR spectrometer at 27 °C. Carr-Purcell-Meiboom-Gill (CPMG) and longitudinal eddy-delay (LED) were applied, resulting in spectra showing only the signals from micro- and macro-metabolites.</p><p><b>RESULTS</b>Compared to controls, rats subjected to CIS showed increased levels of plasma metabolites, such as acetic acid, choline, N-glycoprotein (NAC), saturated fatty acid, and blood sugars. Levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and unsaturated fatty acids were decreased. The biochemical effects of XYS were characterized by elevated levels of VLDL, LDL, threonine, methionine, and glutamic acid in plasma.</p><p><b>CONCLUSION</b>Some common and characteristic metabolites on the anti-CIS of XYP and its modified prescription were obtained. The metabolomics technology is a valuable tool and may be used to identify the specific metabolites and potential biomarkers of therapeutic effect of Chinese medicinal prescriptions.</p>

Expression of AMPA receptors and related protein in immobilization stressed rats and effect of Xiaoyaosan / 中国应用生理学杂志

<p><b>AIM</b>To observe protein expression changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and related regulatory protein in the hippocampus and amygdala in chronic immobilization stressed rat and Xiaoyaosan's regulatory effect.</p><p><b>METHODS</b>Rats were tied 3 h per day to establish immobilization stress condition and treatment with Xiaoyaosan. After 7 days and 21 days stress, the protein expression of AMPA receptor subunit (GluR2/3), N-ethylmaleimide sensitive factor (NSF) and protein interacting with C-kinase 1 (PICK1) in hippocampus and amygdala were detected by using Western blot techniques.</p><p><b>RESULTS</b>The expression of GluR2/3, NSF in dentate gyrus (DG) and amygdala were markedly attenuated (P < 0.05) and PICK1 in CA1 region were significantly increased (P < 0.05) in 7 d immobilization stressed rats while 7 days xiaoyaosan treatment showed an effective regulatory result to PICK1's changes. Under 21 days immobilization stressed condition, the expression of GluR2/3, NSF in CA1 region showed an increasing trend, and GluR2/3 showed a markedly increase (P < 0.01), but showed an significantly decreased trend in amygdala, Xiaoyaosan showed an effective result to such changes above (P < 0.05). The expression of PICK1 showed increasing trend in amygdala and xiaoyaosan could lower its expression (P < 0.05).</p><p><b>CONCLUSION</b>There are different trends of the expression of AMPA receptor in repeat short-term stress versus chronic immobilization stress, and in hippocampal CA1 region versus amygdala. Xiaoyaosan has better regulation effect on the expression of AMPA receptors in the condition of chronic immobilization stress than those of repeat shortterm stress.</p>

Metabonomic study on the regulatory effect of xiaoyao powder on chronic immobilization stressed rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To provide a scientific basis for systematic research on the mechanism of chronic immobilization stress (CIS) induced metabolic network change in rats, through detecting the changes of endogenous metabolites in rats with CIS, treated or un-treated with Xiaoyao Powder (XYP), for determining the small molecule marker compound that closely associated with the metabonomical specificity of CIS and acting mechanism of XYP.</p><p><b>METHODS</b>Thirty-six experimental male SD rats were divided into 3 groups, the normal control group, the model group and the XYP group. And all the three groups were subdivided into two subgroups respectively on day 7 and day 21 of the experiment. The stress rat model of CIS was made by chronic restraining method for 3 h every day. Starting from the first day of modeling, XYP 3.854 g/kg in volume of 1 mL/100 g body weight was administered 1 h before restraining via gastrogavage to rats in the XYP group, while equal volume of distilled water was given to rats in the other two groups instead. Blood samples were collected on the 8 th day and 22 th day for detection in the following procedure: at 27 degrees C, 300 microL supernate of blood plasma was taken, calling the Carr-Purcell-Meiboom-Gill (CPMG) and longitudinal eddy-delay (LED) sequence respectively on a Fourier variable nuclear magnetic resonance (NMR) spectrometer, pre-saturated inhibition of the water peak was performed; free induction decay (FID) signals were transferred via 32 k Fourier transformation to gain one-dimensional NMR spectrogram; by taking TSP as the chemical migration reference peak, the segmental integral calculus (0.04 ppm per segment) was performed from 4.5 - 0.5 ppm (CPMG) and 6.0 - 0 ppm (LED) within the peak ranges in 1H spectra using the VNMR software; after normalization, centering and scaling were conducted on data, then used for pattern recognition of principal component analysis (PCA) using the SIMCA-P 10.0 software, or if necessary, the partial least squares discriminate analysis (PLS-DA) was performed.</p><p><b>RESULTS</b>(1) The metabolites in the model group were significantly different from those in the control group, suggesting that the animal model was successfully established with the metabolic network different to that of control. The model group and the XYP group could be differentiated from the control group by the differences of metabolites and metabolic networks between groups; XYP could intervene the metabolites or the metabolic path to cause changes in final metabolites. (2) The serum contents of lactic acid (1.4, 4.16), choline (3.24), N-acetylgalactosamine (NAC) and saturated fatty acids (1-3) increased, but unsaturated fatty acids (1.99,4-5), blood sugar (34), HDL (0.83), etc. reduced in the CIS rats. XYP showed obvious regulatory effects on final metabolites, causing decrease of lactic acid, choline, NAC, saturated fatty acids and blood sugar, and increase of unsaturated fatty acids, blood sugar, HDL, 3.44 ppm compound, etc.</p><p><b>CONCLUSIONS</b>The metabolic phenotype in CIS rats includes the increase of lactic acid, choline, NAC, saturated fatty acid, and the decrease of blood sugar contents, unsaturated fatty acid, HDL, 3.44 ppm compound, etc., these may be the markers of the metabolites. The final metabolites changes induced by CIS are primarily the lipid substances. XYP markedly regulates the contents of final metabolites, showing the regulatory effects on final metabolites, but what is the metabolite or metabolic pathways it interferes to alter the final metabolites should be confirmed by further studies.</p>

Study on mental stress life events in patients with cyclomastopathy of liver stagnation syndrome type / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the changes of mental stress life events (MSLE) in patients with cyclomastopathy of liver stagnation syndrome type (LSS).</p><p><b>METHODS</b>Clinical epidemiological research method was adopted, the changes of MSLE were observed in cyclomastopathy patients of LSS or non-LSS, classified by syndrome differentiation of TCM.</p><p><b>RESULTS</b>Not only the mean age (33.38 +/- 6.76 years) of patients with LSS was obviously lower than that of patients with non-LSS (38.36 +/- 9.89 years, P < 0.01), but also the mean age of patients with moderate and serious symptoms of LSS (33.96 +/- 7.31 and 37.43 +/- 7.38 years) were higher than that of patients with mild symptoms of LSS (31.67 +/- 5.39 years, P < 0.05 and P < 0.01). MSLE score of patients with LSS (32 scores) was significantly higher than that of patients with non-LSS (22 scores, P < 0.01). MSLE score of patients with moderate and serious LSS was 34.69 +/- 17.78 scores and 51.65 +/- 20.75 scores respectively, both were significantly higher than that of patients with mild LSS (26.57 +/- 15.85 scores, P < 0.05 and P < 0.01).</p><p><b>CONCLUSION</b>The high incidence age of cyclomastopathy is under 40 years, and most of cyclomastopathy patients are classsified to LSS by TCM syndrome differentiation. So age and life event scores may be the objective bases for syndrome typing and liver stagnation syndrome grading in patients with cyclomastopathy.</p>

Effects of Chinese herbs on enkephalin mRNA and prodynorphin mRNA gene expression in rat hippocampus with chronic immobilization stress / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of enkephalin mRNA and prodynorphin mRNA gene expression in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.</p><p><b>METHODS</b>We copied the rat model of chronic immobilization stress (3 h daily , repeated 7 d or 21 d), and primers of enkephalin or prodynorphin were respectively added for RT-PCR reaction (BETA-actin as inner contrast). Gel image analysis system was used to scan and analyze and odds of optical density of target gene and inner contrast strip were taken as quasi-quantified data.</p><p><b>RESULTS</b>Prodynorphin mRNA expression in hippocampus markedly increased in 7 d group (P < 0.01), while enkephalin mRNA prodynorphin mRNA expression in hippocampus markedly increased in 21 d group (P < 0.01). All three recipes were able to decrease the gene expression of prodynorphin mRNA (P < 0.01), and xiaoyao powder as well as sijunzi soup were able to decrease the gene expression of enkephalin mRNA (P < 0.01).</p><p><b>CONCLUSION</b>The effects of xiaoyao powder on the above two gene expression was better than jinkuishenqi pill.</p>

Effects of Chinese herbs on glucocorticoid receptor in rat brain regions with chronic immobilization stress / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of glucocorticoid receptor (GR) in rat brain regions with chronic immobilization stress and the influence of Chinese herbs.</p><p><b>METHODS</b>We copied the rat model of chronic immobilization stress (180 min daily, repeated 7 days or 21 days), and characterized the changes of GR in hippocampus CA1, cortex, dentate gyrus via immunohistochemistry integrated image analysis.</p><p><b>RESULTS</b>The contents of glucocorticoid receptors in hippocampus CA1 , cortex, dentate gyrus were increased and the intensity of immunity reaction was significantly stronger in the model group of 7 days than that in the normal control group (P < 0.05). The contents of GR were significantly decreased and the intensity of immunity reaction was weaken in the model group of 21 days (P < 0.05).</p><p><b>CONCLUSION</b>Compared with the model group of 21 days, the contents of GR were significantly increased and immunity reaction was intensified in three groups of treatment with Chinese herbs (P < 0.05), in which the group treated with soothing-liver herbs Xiaoyaopowder was the best.</p>

Effect of Xiaoyao powder on changes of relative brain zone CRF gene expression in chronic restrained stress rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of Xiaoyao Powder on the content changes of CRF mRNA in relative brain zone (hypothalamus, pituitary, hippocampus, cortex) in chronic restrained stress rats.</p><p><b>METHODS</b>RT-PCR and graphic analysis methods were applied to test the content changes of CRF mRNA in relative brain zone.</p><p><b>RESULTS</b>The CRF-1 gene expression in hypothalamus was modulated lower in stress group and the difference was significant when compared with control group (P < 0.01). The gene expression of CRF-1 in Xiaoyao Powder group was markedly modulated lower in hypothalamus, but it was markedly modulated higher in cortex as compared with control group (P < 0.01). The gene expression of CRF-2 in Xiaoyao Powder group was higher in hypothalamus than that in stress group (P < 0.01), and it was also higher in hippocampus as compared with that in control and stress group (P < 0.01, P < 0.05 respectively).</p><p><b>CONCLUSION</b>The modulation point of Xiaoyao Powder group on central neuropeptide of chronic restrained stress is respectively hypothalamus, pituitary, hippocampus and cortex. The modulating target is hypothalamus, the limbic system and the cortex center. It can be suggested that medicine of smoothing the liver simultaneously have poly-target and dual-modulating action and been involved in the integration function of nerve-endocrine-immune net.</p>