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ObjectiveTo observe the effects of Sinisan on behaviors and NOD-like receptor protein 3 （NLRP3） inflammasomes of depressed rats induced by chronic unpredictable mild stress （CUMS） and further explore the anti-depressant mechanism of Sinisan. MethodFifty male rats were randomly divided into a normal group， a model group， an NLRP3 inhibitor （MCC950） group （10 mg·kg-1）， and low- （2.5 g·kg-1） and high-dose （5 g·kg-1） Sinisan groups， with 10 rats in each group. The depression model was induced by 42 d CUMS in rats except for those in the normal group. Drug intervention was performed on the 22nd day of modeling by gavage in the Sinisan groups and by intraperitoneal injection in the MCC950 group. Except for the MCC950 group， the remaining four groups received 10 mg·kg-1 physiological saline by intraperitoneal injection， while the rats in the model group， the normal group， and the MCC950 group were administered with 3 mL of physiological saline by gavage. Twenty-one days later， the sucrose preference test and open field test were performed. Western blot was used to detect the protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， ionized calcium-binding adapter molecule 1 （Iba1）， and CD68 in the hippocampus of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the hippocampus of rats. Nissl staining and TUNEL were used to assess the pathological changes and apoptosis level in the hippocampal CA1 region of rats， respectively. ResultThe sucrose preference rate and consumption volume in the sucrose preference test， the total distance， the percentage of central movement distance， and the percentage of residence time in the open field test of rats in the model group were lower than those in the normal group （P<0.01）. Compared with the model group， the Sinisan groups and the MCC950 group showed improved depression-like behaviors， apoptosis level in the hippocampal CA1 region， and neuron loss to varying degrees. Sinisan could reduce the levels of IL-1β， IL-18， Bax， Iba1， and CD68 in the hippocampus （P<0.05， P<0.01）， increase the level of Bcl-2 （P<0.05， P<0.01）， and inhibit the protein expression of NLRP3， ASC， and Caspase-1 related to NLRP3 inflammasomes （P<0.05， P<0.01）. ConclusionSinisan can improve the depression-like behaviors and pathological damage of hippocampal neurons in CUMS-induced rats， and the mechanism may be related to the inflammatory response mediated by the NLRP3 inflammasome signaling pathway.
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Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg<sup>-1</sup>） group， and low- （1.25 g·kg<sup>-1</sup>）， medium- （2.5 g·kg<sup>-1</sup>）， and high-dose （5 g·kg<sup>-1</sup>） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.
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Objective:To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress (CUMS) combined with solitary nutrition method based on a depression model. Method:Forty-eight SD male rats were randomly divided into normal group, depression model group, fluoxetine group (1.58 mg·kg-1·d-1), and low, medium and high-dose modified Sinisan (3.67, 7.34, 14.68 g·kg-1·d-1) groups, with 8 rats in each group. After the administration of the model, the levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST） in serum and the levels of inflammatory factors tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β, and IL-6 in liver tissues were measured by a biochemical kit method. Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3 (Caspase-3) and cleaved Caspase-3 in liver cells after intervention with modified Sinisan. Result:Compared with the normal group, the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased (P<0.05), and the levels of inflammatory factors TNF-α, IL-1β and IL-6 in liver tissue significantly increased (P<0.05). Compared with the model group, low, medium-dose modified Sinisan groups significantly reduced serum ALT, AST and inflammatory factors TNF-α, IL-1β and IL-6 levels (P<0.05). Western blot showed that compared with the normal group, the protein expression of Caspase-3 in model rat liver cells decreased, while the protein expression of cleaved Caspase-3 increased（P<0.05，P<0.01）. Compared with the model group, low, medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression, and down-regulated the expression of cleaved Caspase-3 protein（P<0.05，P<0.01）. Conclusion:Chronic stress-induced depression model can cause liver damage. Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological, biochemical and inflammatory factor indicators, and inhibiting liver cell apoptosis.
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Objective:To investigate the mechanism of Sinisan in treating type 2 diabetes mellitus（T2DM） based on network pharmacology. Method:Based on electronic databases， active ingredients of Sinisan and target genes of ingredients as well as type 2 diabetes were screened out. Cytoscape software was applied to construct "herb-active ingredient-target-disease" interaction network diagram，respectively. The common genes of ingredients and disease were uploaded to the STRING database， and the protein interaction network map （PPI） was constructed. CytoNCA and Cluster Marker were used to analyze PPI，respectively. Finally，ClueGO was used to analyze gene ontology （GO） enrichment and Kyoto Encyclopedia of genes and genomes （KEGG） pathway enrichment. Result:A total of 137 active components and 110 effective genes of Sinisan in the treatment of type 2 diabetes were screened out. Based on PPI analysis，these effective genes were divided into 4 different clusters， and 12 genes were considered as the most effective targets. GO enrichment analysis showed that cluster 1 mainly involved acute inflammatory response and acetylcholine receptor signaling pathway， cluster 2 mainly involved cellular response to steroid hormone stimulu and xenobiotic stimulus，and cluster 3 was mainly engaged in the metabolism process of protein，fatty and glucose and the response to hypoxia. KEGG analysis was highly correlated with advanced glycation end products-receptor for AGE （AGE-RAGE） pathway，apoptosis pathway，inflammatory pathway，cell cycles and various metabolic pathways. Conclusion:Sinisan has a regulatory effect in pathogenesis and prognosis of T2DM，such as inflammation，cell apoptosis and nutrition metabolism. Moreover，its potential mechanisms on diabetic angiopathies，diabetic cognitive impairment and cancers were reveal，so as to define a direction for the fundamental research of Sinisan.
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Objective: To discuss the clinical efficacy of modified Sinisan (Qizhi Weitong granule) and saccharomyces boulardi in treating functional dyspepsia (FD) in children, and its effect on changes in serum cytokine and gastrointestinal hormones.Method: Totally 156 cases were divided into control group (78 cases) and observation group (78 cases). The control group was treated with saccharomyces boulardi, 0.25 g, po, bid, after meal. In addition to the therapy of control group, the observation group was also given modified Sinisan (Qizhi Weitong granule), 2.5 g, po, tid, 30 minutes before meal. Four weeks was a course of treatment. Then the clinical efficacy, the time of symptom improvement and the change of serum cytokine and gastrointestinal hormones were observed.Result: The total effective rate of observation group (96.15%) was higher than that of control group (82.05%), with statistical difference (Pγ(IFN-γ), tumor necrosis factor-α(TNF-α), plasma motilin(MTL) and Leptin of both groups had no statistical difference before treatment. After treatment, the serum levels of IL-10, MTL of both group were increased, while the serum levels of IFN-γ, TNF-α, Leptin of both group were decreased. However, the decreasing range and the increasing range of observation group were statistically obvious than those of control group (PConclusion: Modified Sinisan(Qizhi Weitong granule) combined with saccharomyces boulardi have an obvious clinical efficacy in treating child's FD, with a low recurrence. The mechanism may be correlated with the effect of integrated Chinese and Western medicines in regulating serum cytokine and gastrointestinal hormones levels.
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Objective:To investigate the regulatory effect of Sinisan(SNS) on the polarization of RAW264.7 macrophages induced by lipopolysaccharide (LPS). Method:RAW264.7 cells stimulated by LPS were used as the in vitro model. The cells were intervened with the different concentrations of SNS in advance. The effects of different concentrations of SNS on the proliferation of RAW264.7 cells were detected by methyl thiazolyl tetrazolium (MTT) colorimetry. The degree of cell differentiation was detected by enzyme-linked immuno sorbent assay(ELISA) method. The contents of M1 polarization factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and M2 polarization factors interleukin-10 (IL-10) in cell culture supernatant were detected by ELISA method, mRNA levels of M1 polarization factors TNF-α, IL-6 and M2 polarization factors IL-10, arginase-1 (Arg-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) method. Result:SNS had no effect on the cell viability of RAW264.7 cells, inhibited LPS-induced cell proliferation, decreased LPS-stimulated cell differentiation, down-regulated M1 polarizing factors TNF-α, IL-6, IL-1β release and TNF-α, IL-6 mRNA levels, and increased the release of IL-10 and mRNA levels of IL-10 and Arg-1. Conclusion:SNS inhibits the inflammation of RAW264.7 cells induced by LPS, and its mechanism may be related to the regulation of polarization balance of M1/M2 macrophages.
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Objective: To observe the clinical efficacy of Jieyu Tongluo decoction on post-stroke depression (PSD) and its regulatory effect on neurotransmitter. Method: One hundred and twenty-five patients with PSD were randomly divided into control group (62 cases) and observation group (63 cases) by random number table. Both groups got psychological support, health education, and sertraline hydrochloride tablets, 25-50 mg/time, 2 times/days. Patients in control group got Shugan Jieyu capsules, 2 grains/time, 2 times/days. Patients in observation group got Jieyu Tongluo decoction, 1 dose/day. And a course of treatment was 6 weeks. Before and after treatment, hamilton depression scale (HAMD-17), patient health questionnaire-9 (PHQ-9), national institutes of health stroke scale (NHISS),traditional Chinese medicine(TCM) syndrome and activity of daily living scale (ADL) were scored. And levels of 5-serotonin (5-HT), norepinephrine (NE), dopamine (DA), brain-derived neurotrophic factor (BDNF), serum S100-β and neuron enolase (NES) were detected. Result: By rank sum test, after treatment, the clinical efficacy of observation group was superior to that in control group (Z=2.384, PPZ=2.266, PZ=2.817, Pβ and neuron enolase (NES) were lower than those in control group (PPConclusion: In addition to psychotherapy and SSRI, Jieyu Tongluo decoction can relieve degree of depression, depressive symptoms and degree of neurologic impairment, increase activities of daily living, regulate neurotransmitter expression, and improve the reparation of cranial nerve tissue, with obvious clinical effects, and is worthy to be used in clinic.
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Objective: To investigate the clinical efficacy of Yinchenhao Tang combined with Sinisan(YCSN) on non-alcoholic fatty liver disease (NAFLD) with hyperhomocysteinemia (HHcy). Method: Totally 126 cases of NAFLD with HHcy in Beijing Shichahai Community Health Service Center were randomly divided into NAFLD control group, traditional Chinese medicine(TCM) group, and modern medicine group, with 42 cases in each group. The TCM group was treated with YCSN orally, the modern medicine group was treated with polyene phosphatidylcholine capsules and folic acid tablets, and the NAFLD control group was treated with placebo. The course of treatment was 3 months. The clinical efficiency, liver function, Hcy, blood lipid, oxidative inflammation index and symptom score in two groups were observed before and after treatment. Result: The total effective rate of the TCM group was 92.86%, while that of the modern medicine group was 88.10%. There was no significant difference in the clinical efficiency between the two groups. There was no difference in the indexes of groups before treatment. After treatment,alanine aminotransferase (ALT), aspartate aminotransferase (AST), Hcy, total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL), malondialdehyde (MDA), high-sensitive C reactive protein (hs-CRP), serum creatinine (SCr), blood urea nitrogen (BUN), and symptom scores in the TCM group and the modern medicine group were significantly lower than those before the treatment (PPPPPPConclusion: YCSN can improve hyperhomocysteinemia, liver function, blood lipid, oxidation and inflammation in patients with NAFLD and HHcy.
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Pharmacological evaluation on the improvement of sleeping effect usingSi-Ni-San(SNS) in order to conduct further study on scientific connotation of soothing liver-qistagnation. Rats, mice and fruit flies were used as animal model. Pharmacological assessment was conducted and done on the improvement of sleep effect by SNS with the cortical EEG scanning and analysis, biochemistry, molecular pharmacological methodology and technology. SNS can prolong the sleeping time of mice which were induced by pentobarbital sodium. Its effect showed the dose-dependent and time-dependent manner. It can prolong the slow-wave sleep time in normal and sleep deprivation rats. It influenced several neurotransmitters and endogenous sleep factors in brain of normal and sleep deprivation rats. SNS can improve sleeping. The effect was closely related the effect of soothing liver-qi stagnation. The function was realized through multiple pathways and targets.
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Objective To build a method to simultaneously determine paeoniflorin, naringin, hesperidin, glycyrrhizic acid in Sinisan by HPLC, provide a reliable method for evaluation and effective quality control, and lay the foundation of material basis for efficacy research for TCM compound Sinisan.Methods The column was Kromasil C18 (4.6 mm×250 mm, 5μm);mobile phase was acetonitrile-0.05% phosphoric acid aqueous solution with gradient elution program;the flow rate was 1.0 mL/min;UV detection was performed at 240 nm;the detector drift tube temperature was set at 30℃.Results The linear ranges of paeoniflorin, naringin, hesperidin and glycyrrhizic acid were 0.00225-0.01125μg (r=0.999 7), 0.00390-0.00195μg (r=0.9997), 0.00198-0.00099μg (r=0.999 5), 0.00262-0.00131μg (r=0.999 7), respectively. The average recoveries of paeoniflorin, hesperidin, naringin and glycyrrhizic acid were 97.72% (RSD=1.02%), 98.45% (RSD=1.52%), 97.74% (RSD=1.63%), 98.34% (RSD=1.78%), respectively.Conclusion The method is accurate, simple, reliable and duplicable, and is available for the quality control of Sinisan.
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Objective To investigate the effects of Ganmaidazao Decoction (GMDZD), Sinisan(SNS) and Sijunzi Decoction (SJZD) recipe on endogenous nerve growth factor (NGF) of rat with chronic stress.Methods In order to establish the rat models with chronic stress, the feet of animals were stimulated with a pat-tern of electrical impulses (long term, high voltage and constant current). The alterations of behavior of animals were observed and quantified by open-field and tail-suspension test. Levels of NGF in pitttitary,hypetholamus and blood plasma were quantified using radio-immunoassay (RIA) method. Results 1) In comparision with the wild-type (WT) control rats, locomotor activity decreased significantly in the models and groups treated by Chinese medicinal herbs (P<0.01). In addition,the Chinese medicinal herbs treated groups exhibited increased locomotor activity than the model groups (P<0.01). 2) The cross time of the model groups decreased significantly compared with the WT controls (P < 0. 01). Meanwhile, three Chinese medicinal herbs treated groups displayed longer cross time than the model groups (P< 0. 01). 3)The vertical movement times of the model groups decreased significantly compared with the WT controls (P < 0.01). Meanwhile, three Chinese medicinal herbs treated groups displayed in-creased vertical movement times than the model groups (P <0.05). 4)In the tail-suspension test, the duration of immobility increased significantly in the model groups compared with the WT controls (P < 0. 01). However, the duration of immobility of three Chinese medicinal herbs treated groups were less than the model groups (P < 0.01). 5) Compared to the model groups,the level of NGF in pituitary of animals treated by GMDZD and SNS in-creased significantly (P<0.01). In the hypothalamus,the level of NGF in SJZD treated groups decreased in com-parision with the WT control and model groups (P<0.05). Whereas, GMDZD and SNS treated groups decreased significantly than WT control and model groups (P<0.01). In the blood plasma,the level of NGF showed a signif-icant reduction in the model groups compared with the WT control. Conclusion The results suggest that the GM-DZD,SNS and SJZD recipe have positive effects on rat with chronic stress through regulating the level of endogenous NGF.
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Objective To observe the clinical effect of Jiawei Sinisan (JWSNS) on patients with alcohol liver diseases. Methods 80 patients of alcohol liver diseases were divided into two groups, JWSNS and Xiaochaihu (as control) were used respectively to observe the variation of lipoprotein and the expression of hepatic fibrosis markers. Results The symptoms and indicators of patients were improved by JWSNS. The high variation of lipoprotein and the expression of hepatic fibrosis markers were obviously detected on alcohol liver diseases patients who were treated with JWSNS (with an effectivity of 97.5%). However, patients treated with Xiaochaihu had less therapeutic effect. Conclusions JWSNS can obviously regulate the fat metabolism, resist hepatic fibrosis, and improve the symptom of patients suffering from alcohol liver diseases.
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AIM: To observe the effect of Jiawei sinisan (JWSNS) on some amino acids in hippocampus of rats with chronic stress. METHODS: Wistar rats were randomly divided into 3 groups: control, model and JWSNS group. OPA (HPLC) was adopted to detect the contents of amino acids in hippocampus. RESULTS: The contents of Glu and Asp in hippocampus of model group increased significantly ( P
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Objective The chemical components of lyophilized powder of Sinisan were analyzed by the method of RP-HPLC.Methods HPLC Method was applied for quality assessment on lyophilized powder of Sinisan.Column: Kromasil C18 column(250 mm ? 4.6 mm,5 ?m);wavelength: 210 and 240 nm;flow-rate: 1.0 mL/min;column temperature: 28 ℃.Mobile phase: acetonitrile(A) and H2O(acidified to pH=3 with phosphoric acid)(B).Concentration of lyophilized powder of Sinisan was resolved into different parts and analyzed by the same method,the variation of the chemical components was analyzed.Results At 240 nm,21 peaks were detected and two of them were confirmed to be from Bupleurum chinense,three from Paeonla lactiflora,ten from Citrus aurantium,and five from Glycyrrhiza uralensis.At 210 nm,24 peaks were detected and one of them was confirmed to be from B.chinense,four from P.lactiflora,fourteen from C.aurantium,and five form G.uralensis.Conclusion This method can be used to establish the fingerprint chromatograph of lyophilized powder of Sinisan and elucidate the variation of chemical components completely.