Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting b2-adrenergic receptor

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria baicalensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of biophysical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential b2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Hippocampal HMGB1/TLR4 Pathway Mediates Cognitive Dysfunction in Chronic Stress Mice

Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine （5-HT）, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

Chronic stress induces ageing-associated degeneration in rat Leydig cells

Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells. In a pattern similar to the normal process of Leydig cell ageing, stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion. We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells. To test this hypothesis, we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally, intracellular lipofuscin levels, reactive oxygen species （ROS） levels and DNA damage were assessed. The results showed that chronic stress accelerated ageing-related changes： ultrastructural alterations associated with ageing, cellular lipofuscin accumulation, increased ROS levels and more extensive DNA damage were observed. Additionally, testosterone levels were decreased. This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression

Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase （JNK）, protein kinase B （Akt）, and p38 mitogen-activated protein kinase （p38） signal transduction pathway, and also regulate various apoptotic cascades. JNK and p38 promote apoptosis, but Akt protects against apoptosis, in hippocampal neurons. However, changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood. Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group （P 〈 0.05）. No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups, and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups （P 〉 0.05）. These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.

Molecular mechanism of non-alcoholic fatty liver disease induced and aggravated by chronic stress through HSL/ATGL-FFA which promotes fat mobilization

Objective:To study the effects of social stress(CS)and social stress combined with high-fat diet on fat mobilization as a candidate mechanism for the induction or aggravation of non-alcoholic fatty liver disease(NAFLD).Methods:Thirty-two male Wistar rats(250±10 g)were randomly allocated to a blank control group(BC),a high-fat diet group(HFD),a CS group,and a combined CS and high-fat diet group(CS t HFD).Rats were sacrificed and tissues were collected after 8 weeks.Liver and body mass were measured and used to calculate the liver index.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and free fatty acids(FFAs)were measured.Liver sections were examined microscopically after oil red O and hematoxylin and eosin staining.The relative mRNA expression of acetyl-CoA carboxylase(ACCase),hydroxymethylglutaryl coenzyme A(HMG-CoA)reductase in liver,and hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in subcutaneous adipose tissue,were measured by real-time PCR.The liver concentrations of triglyceride,reactive oxygen species,and ACCase were measured by ELISA and HSL activity was determined using turbidimetry.Results:NAFLD developed in the CS,HFD,and CS t HFD groups,with the most severe NAFLD being in the CS t HFD group.Serum AST,ALT,and FFA,liver index,and hepatic triglyceride,FFA,and tumor necrosis factor-a were significantly higher in both the CS and CS t HFD groups.However,food intake and ACCase mRNA expression were lower.The mRNA expression of HSL and ATGL in adipose tissue was much higher,and HSL activity was higher in the CS group than in the BC group,and in the CS t HFD group than in the HFD group.Conclusion:We have successfully established two models of stress-induced NAFLD,suggesting stress can induce and aggravate NAFLD by promoting fat mobilization through upregulation of HSL and ATGL.

Basic fibroblast growth factor improves learning and memory functions in chronic stress mice

Four weeks of uncertain stress was used to establish an animal model of chronic stress. Basic fibroblast growth factor was injected daily for 15 days following stress induction. Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage. Nitric oxide content and calcium concentration were significantly increased in the hippocampus, and learning and memory functions were significantly decreased. After basic fibroblast growth factor intervention, Ca2~ overload was decreased and neuronal damage was relieved in hippocampal neurons, which improved learning and memory functions in chronic stress mice. Latency was prolonged and the number of errors was decreased in a passive avoidance test.

Chronic Stress Induced Proliferation and Activation of Mast Cells of Gastric Antrum in Rats

To explore chronic eration and activation of mast heterotypic stressors induced prolifcells in gastric antrum mucosa by ultrastructure alterations of mast cells, chronic unpredictable heterotypic stressors were used as a study model. The mean immunofluorescence magnitude of mast cell protease 1 （MCP-1） taken from chronic stress rats were 37.4±7.7, significantly higher （p〈0.05） than the value of normal control group （24.8±5.6）. Chronic unpredictable haterotypic stressors appeared also to induce ultrastructure alterations of mast cells. It indicated that mast cells were proliferated and activated, while mast cell granules were hyperplasiaed. Most granules had obvious intragranular changes with loss of electron-dense material. The morphologic evidence showed that macrophages and leukocytes infiltrated in chronic stress rats. Some granules of leukocytes adhered to the surface of mast cell, and formed a bridge. Macrophages phagocytized the mast cell granules.

Antidepressant Effect of Shenwei Ningyu Tablets on Rat Chronic Stress Model and Mouse Tail Suspension Model

[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.

Comparative proteomic analysis of hippocampal proteins from chronic stressed rats

Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic

L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

Beneficial Effects of <i>Fumaria indica</i>on Chronic Stress-Induced Neurobehavioral and Biochemical Perturbations in Rats

Objective: To evaluate the anti-stress activity of standardized extract of Fumaria indica (FI) through validated beha-vioral models of rodents followed by estimation of biochemical changes associated with chronic stress. Methods: Fifty percent ethanolic extract of FI used in this study was standardized on its contents of fumaric acid and its conjugates (0.45% and 0.35% respectively). Stressed Charles Foster rats received unpredictable foot shocks (2 mA, 1 hr, 14 days) through electric grid. FI was given orally as 0.3% carboxymethyl cellulose (CMC) suspension in 100, 200 and 400 mg/kg doses. For comparison, Panax ginseng (PG) extract (100 mg/kg, p.o.) was used as standard adaptogen. Incidence of gastric ulceration, changes in weight of adrenal and spleen, behavioral depression, cognitive dysfunction test and suppression of sexual behavior in male rats were used as validated behavioral models. Plasma corticosterone, brain levels of lipid peroxides (LPO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), and expression of cytokines IL-1β, TNF-α and IL-10 in circulating white blood cells (WBC) were quantified for ascertaining biochemical changes accompanying stress. Results: As compared to vehicle treated stressed rats, the FI and PG treated rats showed fewer incidence of gastric ulceration, reversal of changes in weight of adrenal gland and spleen, reversal of behavioral depression, better performance in passive and active avoidance tests for cognitive function and increased sexual activity. FI and PG significantly decreased chronic unpredictable stress induced elevation of corticosterone, and both extracts normalized also the abnormal oxidative status of the brain observed in stressed rats. FI treatment also suppressed the elevated level of IL-1β, TNF-α and IL-10 in stressed animals. Conclusions: FI could be another adaptogenic herb and fumaric acid and its conjugates are possibly involved in observed bioactivity of its extract.

EFFECTS OF CHRONIC STRESS ON THE ACTIVITIES OF SOD, GSH-Px AND MDA LEVEL IN FEMALE RATS' BRAIN

Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased ( P <0.05 and P <0.01, respectively) while the MDA level increased ( P <0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased ( P <0.05) while the activity in E increased ( P <0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats’ brain.

Chronic stress as an emerging risk factor for the development and progression of glioma

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system.Compared with patients with other cancers,glioma patients often suffer from increased levels of psychological stress,such as anxiety and fear.Chronic stress(CS)is thought to impact glioma profoundly.However,because of the complex mechanisms underlying CS and variability in individual tolerance,the role of CS in glioma remains unclear.This review suggests a new proposal to redivide the stress system into two parts.Neuronal activity is dominant upstream.Stress-signaling molecules produced by the neuroendocrine system are dominant downstream.We discuss the underlying molecular mechanisms by which CS impacts glioma.Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway

Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Effects of Intermittent Hypoxia Exposure on Symptoms of Chronic Fatigue Syndrome in Repeated Restraint Stress and Forced Swimming Induced-Mouse Model

Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.

Simotang enhances gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice

AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.

Effect of an Ilex asprella root decoction on the related genes of lipid metabolism from chronic stress and hyperlipidemic fatty liver in rats

Background The gradually increasing changes in a human hyperlipidemic diet along with chronic stress might play an important role in the increased numbers of fatty liver. This study investigated the effects of Ilex asprella root decoction on related genes of lipid metabolism in chronic stress in hyperlipidemic fatty liver in rats. Methods Forty-eight male Wistar rats were randomly divided into four groups： normal control group, model control group, simvastatin group, and Ilex asprella root group. To establish chronic stress and hyperlipidemic fatty liver models in rats, the levels of serum lipids, glucose, liver index, insulin （INS）, insulin resistant （IR） index, adiponectin, superoxide dismutase （SOD）, glutathione peroxidase （GSH-pX）, glutathione （GSH）, liver X receptor （LXR）, and sterol responsive element binding protein （$REBP）-lc in rats were measured. Results When compared to the normal control group, the levels of serum lipids, glucose, liver index, INS, IR index, and GSH in the model control group significantly increased （P 〈0.01）. The protein levels of LXRa and SREBP-lc increased （P 〈0.05）, and the serum adiponectin and the SOD and GSH-pX decreased significantly （P 〈0.01）. When compared to the model control group, the levels of serum lipids, glucose, liver index, INS, IR index, SOD, and GSH-pX in the simvastatin group and Ilex asprella root group increased in varying degrees （P 〈0.01 or 0.05）; the serum adiponectin and GSH decreased （P 〈0.05）, while the protein levels of LXRa and SREBP-lc decreased in varying degrees （P 〈0.01 or 0.05）. When compared to the simvastatin group, the IR index and protein levels of LXRa in the Ilex asprella root group decreased （P 〈0.05）, and the serum adiponectin and SOD increased （P 〈0.05）. Conclusion The Ilex asprella root decoction has some protective effects on regulating the related genes of lipid metabolism caused by chronic stress and hyperlipidemic fatty liver in rats.