AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1...AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.展开更多
AIM: To evaluate the effect of sumatriptan, a selective 5-HT1 agonist, on anorectal function in irritable bowel syndrome (IBS) patients. METHODS: Twenty-two IBS patients selected according to the Rome II criteria ...AIM: To evaluate the effect of sumatriptan, a selective 5-HT1 agonist, on anorectal function in irritable bowel syndrome (IBS) patients. METHODS: Twenty-two IBS patients selected according to the Rome II criteria (F 15, M 7; mean age 29.3±6.8, range 22-44 years) were examined. The study was blind, randomized and placebo-controlled with a crossover design. Anorectal manometry and rectal balloon distension test were performed before and after the administration of placebo and sumatriptan. RESULTS: The administration of sumatriptan caused a significant increase in the resting anal canal pressure from 9.2±2.0 kPa to 13.1±3.3 kPa (P〈0.0001) connected with the increase in the anal sphincter length and high pressure zone. After sumatriptan injection a remarkable increase in the threshold for the first sensation from 27±9 mL to 34±12 mL (P〈0.05) and urge sensation from 61±19 mL to 68±18 mL (P〈0.01) was observed. Sumatriptan did not affect either the volume evoking the rectoanal inhibitory reflex or the results of the straining test. CONCLUSION: 5-HT1 receptors participate in the regulation of anorectal function. Elucidation of the role of 5-HT1 receptors in the pathophysiological mechanisms of IBS may have some therapeutic implications.展开更多
AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs ...AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.展开更多
Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patient...Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.展开更多
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo...BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.展开更多
Objective:The present study aims to evaluate the in vivo efficacy of YINDARA-4 in improving the symptoms of irritable bowel syndrome(IBS)in a rat model and investigate the impact of YINDARA-4 on potential targets of I...Objective:The present study aims to evaluate the in vivo efficacy of YINDARA-4 in improving the symptoms of irritable bowel syndrome(IBS)in a rat model and investigate the impact of YINDARA-4 on potential targets of IBS management,such as the serotonin level in intestinal tissues and the structure and composition of the gut microbiota.Methods:We developed an IBS rat model by combining stress from maternal separation,acetic acid administration,and restraint.We administered YINDARA-4 water extract to the IBS rat model for 10 consecutive days.The fecal water content,visceral sensitivity,gut microbiota,and serotonin levels in the colonic tissue were then analyzed and compared between the control group,IBS model group,and YINDARA-4–treated groups.Results:Treatment with YINDARA-4 reversed visceral hypersensitivity in a dose-dependent manner in the experimental rat model of IBS.The relief of visceral hypersensitivity upon treatment with YINDARA-4 involved regulation of the gut microbiota structure and composition,and normalization of elevated serotonin levels in the colon.The decrease in colonic serotonin levels with YINDARA-4 treatment might be associated with a reduction in the abundance of Helicobacter and enrichment of Butyricimonas.Conclusions:Treatment with YINDARA-4 was beneficial against visceral hypersensitivity in a rat model of IBS.The improved symptoms exhibited in IBS rats were associated with favorably altered gut microbiota and normalization of serotonin levels in the colon.展开更多
Background The 5-hydroxytryptamine7 receptor (5-HT7 receptor, 5-HTTR) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gas...Background The 5-hydroxytryptamine7 receptor (5-HT7 receptor, 5-HTTR) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT7 receptor in the pathogenesis of IBS. Methods A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0-4℃ cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT7 receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. Results The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P〈0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P〈0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P〈0.05). Real time-PCR results showed that the expression level of the 5-HT7 receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P〈0.05). The expression level of 5-HT7 receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P〈0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P〈0.01 and P〈0.05). The cAMP accumulation in the tBS-C group was higher than that in the control group in the proximal and distal colon (m〈o.o5). Conclusions The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT7 receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.展开更多
Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to ins...Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to insomnia,in order to develop innovative therapies and new compounds.Recently,increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia.Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain.In this review,the role of 5-hydroxytryptamine(5-HT)in insomnia development is summarized,while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes,in order to provide reference for subsequent research.展开更多
5-Hydroxytryptamine 2C(5-HT2C) receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtO H extract of the roots of Bupleurum chinense was...5-Hydroxytryptamine 2C(5-HT2C) receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtO H extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT2 C receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constituents with 5-HT2 C receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d(1), was determined by extensive spectroscopic analyses(HR-ESI-MS, IR, and 1D and 2D NMR). The primary structure-activity relationship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT2 C receptor agonistic activity. Saikosaponin a(3), the main saponin in B. chinense, showed obviously agonistic activity on 5-HT2 C receptor with an EC50 value of 21.08 ± 0.33 μmol×L^(–1) in vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg×kg^(–1) in vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.展开更多
Objective: To observe the influence of acupuncture stimulus and thermal stimulus on the expression of mast cells(MCs) and 5-hydroxytryptamine(5-HT) in local acupoint area of Guanyuan(关元 CV 4) and serum 5-HT in rats....Objective: To observe the influence of acupuncture stimulus and thermal stimulus on the expression of mast cells(MCs) and 5-hydroxytryptamine(5-HT) in local acupoint area of Guanyuan(关元 CV 4) and serum 5-HT in rats.Methods: Thirty-nine male C57 BL/6 rats were randomly divided into blank control group, acupuncture stimulus group and thermal stimulus group, with 13 rats in each group. The rats were stimulated by manual acupuncture at CV 4 for 5 min in acupuncture stimulus group, while those in thermal stimulus group were stimulated by adopting a thermal moxibustion apparatus on CV 4 for 30 min. The expression of MC and 5-HT in the skin in the acupoint area of CV 4 before and after acupuncture stimulus and thermal stimulus was observed and analyzed via adopting toluidine blue staining method and immunofluorescence histochemical method(5 rats were selected from each group), and the 5-HT content in serum before and after stimulus was determined through enzyme-linked immunosorbent assay(ELISA)(8 rats were selected from each group). The influence of acupuncture stimulus and thermal stimulus on the contents of MC and 5-HT in the skin and serum 5-HT in rats was analyzed and compared.Results: ① After acupuncture stimulus or thermal stimulus on CV 4 of C57 BL/6 rats, the number of MC in the acupoint area significantly increased when compared with that in blank group(the acupuncture stimulus group 12.40 ± 2.07 vs. the blank group 3.00 ±5.96;thermal stimulus group 26.20 ± 10.85 vs. the blank group 12.40 ± 2.07, both P< 0.05), and MC aggregation and degranulation were observed(the acupuncture stimulus group 17.80 ±4.55 vs. the blank group 8.00 ±3.16;the thermal stimulus group24.00±9.05 vs. the blank group 8.00±3.16. P<0.05, P< 0.01).② After acupuncture stimulus or thermal stimulus, 5-HT was released by MCs in the acupoint area, which aggregated around the blood vessels,and the number of 5-HT in the acupoint area significantly increased when compared with that in blank group(the blank group 3.00 ±1.28 vs. the acupuncture stimulus group 10.02 ±3.21;the blank group3.00 ±1.28 vs. the thermal stimulus group 14.00 ±3.94, both P< 0.01).③ Compared with blank group,both acupuncture stimulus and thermal stimulus could reduce the 5-HT content in serum(the blank group 0.72 ±0.2372 vs. acupuncture stimulus group 0.43 ±0.21: the blank group 0.72 ±0.24 vs. thermal stimulus group 0.32 ±0.18, both P<0.01), and the effect in thermal stimulus group was slightly superior to that in acupuncture stimulus group(P<0.05).Conclusion: Both acupuncture stimulus and thermal stimulus can cause the aggregation and degranulation of MCs and high expression of 5-HT in the acupoint area. The effect of thermal stimulus was superior to that of acupuncture stimulus in degranulation.展开更多
The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium inf...The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.展开更多
Objective: To observe the changes of 5-hydroxytryptamine (5-HT) in colonic membrane of diarrhea-predominant irritable bowel syndrome (IBS-D) and the clinical efficacy of herbal cake-partitioned moxibustion in tre...Objective: To observe the changes of 5-hydroxytryptamine (5-HT) in colonic membrane of diarrhea-predominant irritable bowel syndrome (IBS-D) and the clinical efficacy of herbal cake-partitioned moxibustion in treating it, and to explore the action mechanisms. Methods: Seventy-three subjects were randomized into two groups: moxibustion group in which 37 cases were treated by herbal cake-partitioned moxibustion and needling group in which 36 cases were treated by needling. The clinical efficacy and 5-HT expression in colonic membrane were observed. Results: The cure rate was 43.2% in the moxibustion group and 36.1% in the needling group, with no significant difference between the two groups (P〉0.05). Herbal cake-partitioned moxibustion could reduce 5-HT expression in colonic membrane. Conclusion: Herbal cake-partitioned moxibustion might improve the clinical symptoms of IBS-D by reducing 5-HT expression.展开更多
Objective To investigate the effects of echinacoside on the extracellular striatal levels of norepinephrine(NE),dopamine(DA),homovanillic acid(HVA),3,4-dihydroxyphenylethanoid acid(DOPAC),5-hydroxyindoleacetic...Objective To investigate the effects of echinacoside on the extracellular striatal levels of norepinephrine(NE),dopamine(DA),homovanillic acid(HVA),3,4-dihydroxyphenylethanoid acid(DOPAC),5-hydroxyindoleacetic acid(HIAA),and 5-hydroxytryptamine(5-HT) in middle cerebral artery occlusion(MCAO rats.Methods The middle cerebral artery was occluded in male Sprague-Dawley rats.Three days later microdialysis probes were placed into the right striatum of MCAO rat brains and the brains were perfused with Ringer's solution at a rate of 1.5 μL/min.Cerebral microdialysates were collected every 30 minutes from awake and freely moving rats before assaying for NE,DA,HVA,DOPAC,HIAA,and 5-HT levels by reverse phase HPLC with electrochemistry.Results Three days after MCAO,the extracellular striatal levels of NE,DA,DOPAC,HIAA,HVA,and 5-HT of the MCAO rats increased significantly(at least P0.05 vs.control).However,simultaneous treatment with echinacoside(30.0 or 15.0 mg/kg) attenuated these increases(at least P0.05 vs.non-treated model rats).Conclusion These results imply that echinacoside may protect striatal dopa minergic neurons from the injury induced by MCAO and may help prevent and treat cerebral ischemic diseases.展开更多
Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pa...Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pathway.Methods(i)In vivo experiments:60 specified pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into six groups with 10 rats in each groups:control,DD model,positive(1.8 mg/kg fluoxetine+0.18 g/kg metformin),high-dose ZGJTJYF(ZGJTJYFH,40.500 g/kg ZGJTJYF),middle-dose ZGJTJYF(ZGJTJYF-M,20.250 g/kg ZGJTJYF),and lowdose ZGJTJYF(ZGJTJYF-L,10.125 g/kg ZGJTJYF)groups.Except for the control group,other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin(STZ)and four weeks of chronic unpredictable mild stress(CUMS).All drug administration groups were treated by gavage during CUMS modeling,and the control and model groups were given equal amount of distilled water.After four weeks,the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF.Moreover,the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF.Changes in 5-hydroxytryptamine(5-HT)level were detected via high-performance liquid chromatography with electrochemical detection(HPLC-ECD);the levels of tryptophan(TRP),kynurenine(KYN),and indoleamine 2,3-dioxygenase(IDO)in the hippocampus were detected using enzyme-linked immunosorbent assay(ELISA);the protein expression levels of synaptophysin(SYN)and postsynaptic density material-95(PSD-95)were detected via immunohistochemistry(IHC);and the protein expression levels of N-methyl-D-aspartate receptor(NR)2 A and NR2 B were detected using Western blot.(ii)In vitro experiments:five SPF grade SD pregnant rats(E16–18)were used to obtain primary hippocampal neurons(Ne),six SD new-born rats were used to collected primary astrocytes(As)and microglia(MG),and to establish a Ne-As-MG co-culture system.All co-culture systems were divided into six groups:control(PBS),model[150 mmol/L glucose+200μmol/L corticosterone(G&P)+PBS],blank(G&P+blank serum),positive(G&P+positive drug-containing serum),ZGJTJYF(G&P+ZGJTJYF serum),and 1-methyl-D-tryptophan(1-MT,IDO inhibitor)(G&P+1-MT)groups.After 18 h of intervention by corresponding treatment,immunofluorescence was used to analyze the protein expression levels of SYN,PSD-95,NR2 A,and NR2 B;ELISA was performed to measure the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and TRP/KYN metabolic pathway-related factors[TRP,KYN,kynurenine acid(KYNA),quinolinic acid(QUIN)].Results(i)In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats(P<0.01 and P<0.05,respectively);ZGJTJYF-H,ZGJTJYF-M,and ZGJTJYF-L increased their autonomous activity,learning,and memory ability(P<0.01,P<0.01,and P<0.05,respectively).Moreover,the levels of 5-HT and TRP were significantly increased(P<0.01),and the levels of KYN and IDO were significantly decreased in the hippocampus(P<0.01)of rats after ZGJTJYF-M treatment.The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons(P<0.01),while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus(P<0.05)of rats after ZGJTJYF-M treatment.(ii)In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons(P<0.01),decreased the levels of IL-1β(P<0.01),IL-6(P<0.05),TNF-α(P<0.01),IDO(P<0.05),KYN(P<0.05),and QUIN(P<0.01),and increased the levels of TRP and KYNA(P<0.01)in the simulated DD state.ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons(P<0.05)in a stimulated DD state.Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway,and it has a favorable protective effect on hippocampal neuron injury caused by DD.Therefore,ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.展开更多
[Objectives]This paper aimed to investigate the effect of Tuina combined with sling exercise therapy(SET)and psoas&abdominal training on serum 5-hydroxytryptamine(5-HT)andβ-endorphin(β-EP)levels in patients with...[Objectives]This paper aimed to investigate the effect of Tuina combined with sling exercise therapy(SET)and psoas&abdominal training on serum 5-hydroxytryptamine(5-HT)andβ-endorphin(β-EP)levels in patients with nonspecific low back pain(NLBP).[Methods]Total 46 patients with NLBP who visited the Tuina Department of the First Affiliated Hospital of Hainan Medical University from August 2019 to May 2020 were randomly and evenly divided into control group and treatment group.On the basis of Tuina therapy,the patients in the control group and treatment group were treated with psoas&abdominal training and SET,respectively.After the treatment,the serum 5-HT andβ-EP levels of the patients were detected.[Results]The serum 5-HT andβ-EP levels in the treatment group were significantly improved compared with the control group(P<0.05).[Conclusions]The nerve&muscle reconstruction techniques of Tuina combined with SET or psoas&abdominal training can improve serum 5-HT andβ-EP levels in patients with NLBP.展开更多
Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron...Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron hydrochloride alone in patients with chemotherapy.Methods:Sixty-four patients were randomized to receive either granisetron hydrochloride alone (control group:granisetron hydrochloride 3 mg intervenous infusion before chemotherapy, from the 1st day of chemotherapy course until the day after chemotherapy course completed) or magnetotherapy plus granisetron hydrochloride (treatment group:the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 every day after chemotherapy for 5 begin with chemotherapy).Baseline characteristics were similar in both groups.The patients' emesia was evaluated according to WHO's criteria.The density of 5-HT3 was detected by enzyme-linked immunosorbent assay (ELISA).Results:In the treatment of acute vomiting, there was no significant difference between two groups (P>0.05), but in the treatment of tardive vomiting, the effectiveness in treatment group was better than that in control group (P<0.05).The density of 5-HT3 in treatment group and control group were (225.32±57.29) ng/mL vs (213.00 ±53.29) ng/mL before chemotherapy and (273.88 ±75.42) ng/mL vs (313.17±76.36) ng/mL after chemotherapy (P<0.01); the rate of adverse events was 36.36% and 48.39% respectively in treatment group and control group (P>0.05).Conclusion:Magnetotherapy plus granisetron hydrochloride provide better effectiveness than granisetron hydrochloride alone, and both therapies have synergistic effect.The adverse events didn't raised in treatment group.展开更多
基金Supported by National Education Department"ChunHui Plan"Research Projects,No.Z2010021China Postdoctoral Science Foundation Project,No.2013M531079+2 种基金Heilongjiang Postdoctoral Funding Project,No.LBH-Z12246Heilongjiang Education Department Scientific Research Project,No.12521502excellent Innovative Talents Support Program Funding of Heilongjiang University of Chinese Medicine(Outstanding Young Academic Leaders),No.051217
文摘AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
基金Supported by the grant from GlaxoSmithKline Pharmaceuticals S.A.
文摘AIM: To evaluate the effect of sumatriptan, a selective 5-HT1 agonist, on anorectal function in irritable bowel syndrome (IBS) patients. METHODS: Twenty-two IBS patients selected according to the Rome II criteria (F 15, M 7; mean age 29.3±6.8, range 22-44 years) were examined. The study was blind, randomized and placebo-controlled with a crossover design. Anorectal manometry and rectal balloon distension test were performed before and after the administration of placebo and sumatriptan. RESULTS: The administration of sumatriptan caused a significant increase in the resting anal canal pressure from 9.2±2.0 kPa to 13.1±3.3 kPa (P〈0.0001) connected with the increase in the anal sphincter length and high pressure zone. After sumatriptan injection a remarkable increase in the threshold for the first sensation from 27±9 mL to 34±12 mL (P〈0.05) and urge sensation from 61±19 mL to 68±18 mL (P〈0.01) was observed. Sumatriptan did not affect either the volume evoking the rectoanal inhibitory reflex or the results of the straining test. CONCLUSION: 5-HT1 receptors participate in the regulation of anorectal function. Elucidation of the role of 5-HT1 receptors in the pathophysiological mechanisms of IBS may have some therapeutic implications.
文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.
文摘Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.
基金results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu)currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)
文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
基金funded by the foundation of the Key Laboratory of Ethnomedicine(Minzu University of China),the Ministry of Education(KLEM-ZZ201903,KLEM-ZZ2020GD01)the Natural Science Foundation of Ningxia(2021AAC03358)funded by the National Natural Science Foundation of China(81901682)
文摘Objective:The present study aims to evaluate the in vivo efficacy of YINDARA-4 in improving the symptoms of irritable bowel syndrome(IBS)in a rat model and investigate the impact of YINDARA-4 on potential targets of IBS management,such as the serotonin level in intestinal tissues and the structure and composition of the gut microbiota.Methods:We developed an IBS rat model by combining stress from maternal separation,acetic acid administration,and restraint.We administered YINDARA-4 water extract to the IBS rat model for 10 consecutive days.The fecal water content,visceral sensitivity,gut microbiota,and serotonin levels in the colonic tissue were then analyzed and compared between the control group,IBS model group,and YINDARA-4–treated groups.Results:Treatment with YINDARA-4 reversed visceral hypersensitivity in a dose-dependent manner in the experimental rat model of IBS.The relief of visceral hypersensitivity upon treatment with YINDARA-4 involved regulation of the gut microbiota structure and composition,and normalization of elevated serotonin levels in the colon.The decrease in colonic serotonin levels with YINDARA-4 treatment might be associated with a reduction in the abundance of Helicobacter and enrichment of Butyricimonas.Conclusions:Treatment with YINDARA-4 was beneficial against visceral hypersensitivity in a rat model of IBS.The improved symptoms exhibited in IBS rats were associated with favorably altered gut microbiota and normalization of serotonin levels in the colon.
基金the key clinical project of Chinese Ministry of Health(2004-2006).
文摘Background The 5-hydroxytryptamine7 receptor (5-HT7 receptor, 5-HTTR) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT7 receptor in the pathogenesis of IBS. Methods A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0-4℃ cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT7 receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. Results The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P〈0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P〈0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P〈0.05). Real time-PCR results showed that the expression level of the 5-HT7 receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P〈0.05). The expression level of 5-HT7 receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P〈0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P〈0.01 and P〈0.05). The cAMP accumulation in the tBS-C group was higher than that in the control group in the proximal and distal colon (m〈o.o5). Conclusions The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT7 receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.
基金supported by the National Natural Science Foundation of China(Nos.82174091,82122066,81973291,and 82003909)the National Key R&D Program of China(No.2022YFC2704603).
文摘Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to insomnia,in order to develop innovative therapies and new compounds.Recently,increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia.Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain.In this review,the role of 5-hydroxytryptamine(5-HT)in insomnia development is summarized,while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes,in order to provide reference for subsequent research.
基金supported by the National Science Foundation of China(No.81573322)the Hundred-Talent Program of CAS+1 种基金the CAS"Light of West China"Programthe Youth Innovation Promotion Association of CAS
文摘5-Hydroxytryptamine 2C(5-HT2C) receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtO H extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT2 C receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constituents with 5-HT2 C receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d(1), was determined by extensive spectroscopic analyses(HR-ESI-MS, IR, and 1D and 2D NMR). The primary structure-activity relationship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT2 C receptor agonistic activity. Saikosaponin a(3), the main saponin in B. chinense, showed obviously agonistic activity on 5-HT2 C receptor with an EC50 value of 21.08 ± 0.33 μmol×L^(–1) in vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg×kg^(–1) in vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.
文摘Objective: To observe the influence of acupuncture stimulus and thermal stimulus on the expression of mast cells(MCs) and 5-hydroxytryptamine(5-HT) in local acupoint area of Guanyuan(关元 CV 4) and serum 5-HT in rats.Methods: Thirty-nine male C57 BL/6 rats were randomly divided into blank control group, acupuncture stimulus group and thermal stimulus group, with 13 rats in each group. The rats were stimulated by manual acupuncture at CV 4 for 5 min in acupuncture stimulus group, while those in thermal stimulus group were stimulated by adopting a thermal moxibustion apparatus on CV 4 for 30 min. The expression of MC and 5-HT in the skin in the acupoint area of CV 4 before and after acupuncture stimulus and thermal stimulus was observed and analyzed via adopting toluidine blue staining method and immunofluorescence histochemical method(5 rats were selected from each group), and the 5-HT content in serum before and after stimulus was determined through enzyme-linked immunosorbent assay(ELISA)(8 rats were selected from each group). The influence of acupuncture stimulus and thermal stimulus on the contents of MC and 5-HT in the skin and serum 5-HT in rats was analyzed and compared.Results: ① After acupuncture stimulus or thermal stimulus on CV 4 of C57 BL/6 rats, the number of MC in the acupoint area significantly increased when compared with that in blank group(the acupuncture stimulus group 12.40 ± 2.07 vs. the blank group 3.00 ±5.96;thermal stimulus group 26.20 ± 10.85 vs. the blank group 12.40 ± 2.07, both P< 0.05), and MC aggregation and degranulation were observed(the acupuncture stimulus group 17.80 ±4.55 vs. the blank group 8.00 ±3.16;the thermal stimulus group24.00±9.05 vs. the blank group 8.00±3.16. P<0.05, P< 0.01).② After acupuncture stimulus or thermal stimulus, 5-HT was released by MCs in the acupoint area, which aggregated around the blood vessels,and the number of 5-HT in the acupoint area significantly increased when compared with that in blank group(the blank group 3.00 ±1.28 vs. the acupuncture stimulus group 10.02 ±3.21;the blank group3.00 ±1.28 vs. the thermal stimulus group 14.00 ±3.94, both P< 0.01).③ Compared with blank group,both acupuncture stimulus and thermal stimulus could reduce the 5-HT content in serum(the blank group 0.72 ±0.2372 vs. acupuncture stimulus group 0.43 ±0.21: the blank group 0.72 ±0.24 vs. thermal stimulus group 0.32 ±0.18, both P<0.01), and the effect in thermal stimulus group was slightly superior to that in acupuncture stimulus group(P<0.05).Conclusion: Both acupuncture stimulus and thermal stimulus can cause the aggregation and degranulation of MCs and high expression of 5-HT in the acupoint area. The effect of thermal stimulus was superior to that of acupuncture stimulus in degranulation.
基金supported by the National Natural Science Foundation of China(Nos.81971943,81772196,31470264,81271820,30870789,and 30300117)the Stanley Foundation from the Stanley Medical Research Institute(SMRI),United States(No.06R-1366)We acknowledge the Medicine Research Center for Structural Biology of Wuhan University for providing the confocal microscopy(Leica-LCS-SP8-STED).
文摘The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.
基金State Administration of TCM of RR.China(2003ZL23)Shanghai Leading Academic Discipline Project
文摘Objective: To observe the changes of 5-hydroxytryptamine (5-HT) in colonic membrane of diarrhea-predominant irritable bowel syndrome (IBS-D) and the clinical efficacy of herbal cake-partitioned moxibustion in treating it, and to explore the action mechanisms. Methods: Seventy-three subjects were randomized into two groups: moxibustion group in which 37 cases were treated by herbal cake-partitioned moxibustion and needling group in which 36 cases were treated by needling. The clinical efficacy and 5-HT expression in colonic membrane were observed. Results: The cure rate was 43.2% in the moxibustion group and 36.1% in the needling group, with no significant difference between the two groups (P〉0.05). Herbal cake-partitioned moxibustion could reduce 5-HT expression in colonic membrane. Conclusion: Herbal cake-partitioned moxibustion might improve the clinical symptoms of IBS-D by reducing 5-HT expression.
基金supported by the National Natural Science Foundation of China (No.30560171,No.30860334)
文摘Objective To investigate the effects of echinacoside on the extracellular striatal levels of norepinephrine(NE),dopamine(DA),homovanillic acid(HVA),3,4-dihydroxyphenylethanoid acid(DOPAC),5-hydroxyindoleacetic acid(HIAA),and 5-hydroxytryptamine(5-HT) in middle cerebral artery occlusion(MCAO rats.Methods The middle cerebral artery was occluded in male Sprague-Dawley rats.Three days later microdialysis probes were placed into the right striatum of MCAO rat brains and the brains were perfused with Ringer's solution at a rate of 1.5 μL/min.Cerebral microdialysates were collected every 30 minutes from awake and freely moving rats before assaying for NE,DA,HVA,DOPAC,HIAA,and 5-HT levels by reverse phase HPLC with electrochemistry.Results Three days after MCAO,the extracellular striatal levels of NE,DA,DOPAC,HIAA,HVA,and 5-HT of the MCAO rats increased significantly(at least P0.05 vs.control).However,simultaneous treatment with echinacoside(30.0 or 15.0 mg/kg) attenuated these increases(at least P0.05 vs.non-treated model rats).Conclusion These results imply that echinacoside may protect striatal dopa minergic neurons from the injury induced by MCAO and may help prevent and treat cerebral ischemic diseases.
基金National Natural Science Foundation of China(81874464and 82104793)the Scientific Research Project of Education Department of Hunan Province(19K066)。
文摘Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pathway.Methods(i)In vivo experiments:60 specified pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into six groups with 10 rats in each groups:control,DD model,positive(1.8 mg/kg fluoxetine+0.18 g/kg metformin),high-dose ZGJTJYF(ZGJTJYFH,40.500 g/kg ZGJTJYF),middle-dose ZGJTJYF(ZGJTJYF-M,20.250 g/kg ZGJTJYF),and lowdose ZGJTJYF(ZGJTJYF-L,10.125 g/kg ZGJTJYF)groups.Except for the control group,other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin(STZ)and four weeks of chronic unpredictable mild stress(CUMS).All drug administration groups were treated by gavage during CUMS modeling,and the control and model groups were given equal amount of distilled water.After four weeks,the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF.Moreover,the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF.Changes in 5-hydroxytryptamine(5-HT)level were detected via high-performance liquid chromatography with electrochemical detection(HPLC-ECD);the levels of tryptophan(TRP),kynurenine(KYN),and indoleamine 2,3-dioxygenase(IDO)in the hippocampus were detected using enzyme-linked immunosorbent assay(ELISA);the protein expression levels of synaptophysin(SYN)and postsynaptic density material-95(PSD-95)were detected via immunohistochemistry(IHC);and the protein expression levels of N-methyl-D-aspartate receptor(NR)2 A and NR2 B were detected using Western blot.(ii)In vitro experiments:five SPF grade SD pregnant rats(E16–18)were used to obtain primary hippocampal neurons(Ne),six SD new-born rats were used to collected primary astrocytes(As)and microglia(MG),and to establish a Ne-As-MG co-culture system.All co-culture systems were divided into six groups:control(PBS),model[150 mmol/L glucose+200μmol/L corticosterone(G&P)+PBS],blank(G&P+blank serum),positive(G&P+positive drug-containing serum),ZGJTJYF(G&P+ZGJTJYF serum),and 1-methyl-D-tryptophan(1-MT,IDO inhibitor)(G&P+1-MT)groups.After 18 h of intervention by corresponding treatment,immunofluorescence was used to analyze the protein expression levels of SYN,PSD-95,NR2 A,and NR2 B;ELISA was performed to measure the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and TRP/KYN metabolic pathway-related factors[TRP,KYN,kynurenine acid(KYNA),quinolinic acid(QUIN)].Results(i)In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats(P<0.01 and P<0.05,respectively);ZGJTJYF-H,ZGJTJYF-M,and ZGJTJYF-L increased their autonomous activity,learning,and memory ability(P<0.01,P<0.01,and P<0.05,respectively).Moreover,the levels of 5-HT and TRP were significantly increased(P<0.01),and the levels of KYN and IDO were significantly decreased in the hippocampus(P<0.01)of rats after ZGJTJYF-M treatment.The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons(P<0.01),while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus(P<0.05)of rats after ZGJTJYF-M treatment.(ii)In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons(P<0.01),decreased the levels of IL-1β(P<0.01),IL-6(P<0.05),TNF-α(P<0.01),IDO(P<0.05),KYN(P<0.05),and QUIN(P<0.01),and increased the levels of TRP and KYNA(P<0.01)in the simulated DD state.ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons(P<0.05)in a stimulated DD state.Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway,and it has a favorable protective effect on hippocampal neuron injury caused by DD.Therefore,ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.
基金Natural Science Foundation of Hainan Province(No.818QN248,No.818MS061)。
文摘[Objectives]This paper aimed to investigate the effect of Tuina combined with sling exercise therapy(SET)and psoas&abdominal training on serum 5-hydroxytryptamine(5-HT)andβ-endorphin(β-EP)levels in patients with nonspecific low back pain(NLBP).[Methods]Total 46 patients with NLBP who visited the Tuina Department of the First Affiliated Hospital of Hainan Medical University from August 2019 to May 2020 were randomly and evenly divided into control group and treatment group.On the basis of Tuina therapy,the patients in the control group and treatment group were treated with psoas&abdominal training and SET,respectively.After the treatment,the serum 5-HT andβ-EP levels of the patients were detected.[Results]The serum 5-HT andβ-EP levels in the treatment group were significantly improved compared with the control group(P<0.05).[Conclusions]The nerve&muscle reconstruction techniques of Tuina combined with SET or psoas&abdominal training can improve serum 5-HT andβ-EP levels in patients with NLBP.
基金Supported by a grant from the Government Science and Technology Agency of Zhejiang Province (No.2006C23018)
文摘Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron hydrochloride alone in patients with chemotherapy.Methods:Sixty-four patients were randomized to receive either granisetron hydrochloride alone (control group:granisetron hydrochloride 3 mg intervenous infusion before chemotherapy, from the 1st day of chemotherapy course until the day after chemotherapy course completed) or magnetotherapy plus granisetron hydrochloride (treatment group:the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 every day after chemotherapy for 5 begin with chemotherapy).Baseline characteristics were similar in both groups.The patients' emesia was evaluated according to WHO's criteria.The density of 5-HT3 was detected by enzyme-linked immunosorbent assay (ELISA).Results:In the treatment of acute vomiting, there was no significant difference between two groups (P>0.05), but in the treatment of tardive vomiting, the effectiveness in treatment group was better than that in control group (P<0.05).The density of 5-HT3 in treatment group and control group were (225.32±57.29) ng/mL vs (213.00 ±53.29) ng/mL before chemotherapy and (273.88 ±75.42) ng/mL vs (313.17±76.36) ng/mL after chemotherapy (P<0.01); the rate of adverse events was 36.36% and 48.39% respectively in treatment group and control group (P>0.05).Conclusion:Magnetotherapy plus granisetron hydrochloride provide better effectiveness than granisetron hydrochloride alone, and both therapies have synergistic effect.The adverse events didn't raised in treatment group.