Effects of moxibustion of "biaoben acupoint combination" on heart rate variability, atrial natriuretic peptide in the model rats of IBS-D complicated with anxiety / 中国针灸

OBJECTIVE@#To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination".@*METHODS@#Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence.@*RESULTS@#Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group.@*CONCLUSION@#Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.

Clinical Efficacy of Tongxie Yaofang on Diarrhea-predominant Irritable Bowel Syndrome （IBS-D） Patients with Liver Depression and Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and mechanism of Tongxie Yaofang in treating diarrhea-predominant irritable bowel syndrome（IBS-D） patients with liver depression and spleen deficiency. MethodA total of 168 IBS-D patients with liver depression and spleen deficiency who were treated from August 2017 to June 2021 were divided into observation group and control group by random number table，84 in each group. The observation group was administrated with Tongxie Yaofang decoction-free granules orally，and the control group received oral treatment of pinaverium bromide，both for 4 weeks. The main symptoms of IBS were compared before and after treatment，such as the degree of abdominal pain，stool changes，traditional Chinese medicine pattern curative effect scoring system（TCM-PES），IBS quality of life questionnaire （IBS-QOL），IBS symptom severity scale（IBS-SSS），self-rating anxiety scale （SAS），and self-rating depression scale（SDS）. Nimodipine was used to evaluate the efficacy based on TCM syndrome score of liver depression and Qi stagnation. Enzyme-linked immunosorbent assay（ELISA） was conducted to detect the plasma interleukin-10（IL-10）and IL-12 before and after treatment. ResultAfter 4 weeks of treatment， the response rate of abdominal pain in observation group was 92.86% （78/84）， higher than that in control group （82.14%， 69/84）（χ2=6.254，P<0.05）. The response rates of diarrhea in observation group and control group were 91.67% （77/84）and 77.38% （65/84）， respectively（χ2=8.214，P<0.01）. TCM-PES and IBS-QOL scores of observation group after treatment were higher and IBS-SSS score was lower than those of control group （P<0.05）. The efficacy rate of TCM syndromes in observation group was higher than that of control group （P<0.05）. Additionally， after treatment， the observation group had lower SAS and SDS scores （P<0.05）and IL-12 level（P<0.05）and higher plasma IL-10 level than the control group （P<0.05）. ConclusionTongxie Yaofang can relieve abdominal pain and diarrhea in IBS-D patients with liver depression and spleen deficiency，reduce negative emotion，and improve the quality of life of patients，which may be related to alleviating the visceral hypersensitivity.

Effect of Valeriana jatamansi extract on fecal UPLC-MS/MS metabolomics in rats with diarrheal irritable bowel syndrome / 中国中药杂志

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.

Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating / 中国针灸

OBJECTIVE@#To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating @*METHODS@#A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating @*RESULTS@#After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (@*CONCLUSION@#Acupuncture for regulating

Efficacy and mechanism of acupuncture combined with for diarrhea-type irritable bowel syndrome of liver depression and spleen deficiency / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture at lower- acupoints and front- acupoints combined with (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism.@*METHODS@#A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared.@*RESULTS@#After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (<0.05).@*CONCLUSION@#The acupuncture at lower- acupoints and front- acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.

Clinical Efficacy and Mechanism of Tongxie Yaofang on Patients with IBS-D of Liver Depression and Spleen Deficiency / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Tongxie Yaofang on irritable bowel syndrome-D (IBS-D) of liver-stagnation and spleen-deficiency type, in order to explore its mechanism in regulating brain-intestine interaction by changing the intestinal flora before and after treatment. Method:Totally 116 patients with IBS-D with liver stagnation and spleen deficiency who were diagnosed from July 2016 to December 2018 were randomly divided into observation group and control group, with 58 patients in each group. Observation group was treated with Tongxie Yaofang orally. Control group was treated with pivalvonium orally. Both groups were treated for 4 weeks. Scores of traditional Chinese medicine pattern curative effect scoring system (TCM-PES), IBS quality of life questionnaire (IBS-QOL), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of two groups were compared before and after treatment. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were detected before and after treatment by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) was used to detect changes in Escherichia coli, Bifidobacteria, Lactobacillus acidophilus and Streptococcus faecalis and other intestinal flora before and after treatment. Result:TCM-PES and IBS-QOL scores of two groups were improved after treatment. TCM-PES and IBS-QOL scores of observation group were higher than those of control group (P<0.05). TCM syndromes of observation group were significantly higher than those of control group (P<0.05). SAS and SDS scores were significantly lower after treatment. SAS and SDS scores of observation group were lower than those of control group after treatment (P<0.05). Plasma CGRP and VIP decreased after treatment. Plasma CGRP and VIP in observation group were significantly lower than those in control group (P<0.05). There was no significant change in E. coli after treatment in two groups. After treatment, L. acidophilus, Bifidobacterium, and S. faecalis increased (P<0.05). In control group, intestinal L. acidophilus increased after treatment (P<0.05). The differences of intestinal L. acidophilus, Bifidobacterium, S. faecalis in two groups were statistically significant (P<0.05). Conclusion:TCM can alleviate clinical symptoms, such as abdominal pain and diarrhea in patients with IBS-D, improve patients' bad mood and improve their quality of life. This may be related to improvement of intestinal flora imbalance, regulation of brain intestinal peptide secretion and reduction of visceral hypersensitivity.

Research Progress on Mechanism of Tongxie Yaofang in Treating Diarrhea-Predominate Irritable Bowel Syndrome Based on Brain-gut Interaction Function / 中国实验方剂学杂志

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the common functional gastrointestinal diseases in clinical practice, its pathogenesis is diverse. Because of its sudden and lingering intractable symptoms, it seriously affects patients' work and life. IBS-D patients suffer from repeated illnesses, which often affect their lives with mental symptoms such as anxiety and depression. Anxiety and depression can also affect visceral sensation, increase intestinal sensitivity, aggravated by interaction between physical symptoms and mental symptoms. The main pathogenesis of IBS-D such as visceral hypersensitivity, gastrointestinal motility disorders, intestinal infections, and psychosocial factors are all related to brain-gut interaction disorders. Patients with IBS-D are prone to brain-gut interaction disorders due to long-term chronic mental stress. Brain-gut interaction is the main mode of regulation of gastrointestinal function in the brain-gut axis. Traditional Chinese medicine （TCM） believes that the main syndrome type of IBS-D patients is liver stagnation and spleen deficiency, while liver stagnation will be unsatisfactory, and the secretion and content of various neurotransmitters in the brain are closely related to emotions. Tongxie Yaofang is a commonly basic prescription used for the clinical treatment of IBS-D liver stagnation and spleen deficiency syndrome. It has the functions of softening the liver and replenishing the spleen, removing dampness and stopping diarrhea, and has a significant clinical effect. At present, many animal experiments and clinical studies have explored the mechanism of Tongxie Yaofang in treating IBS-D and its effect on brain-gut interaction function and brain-gut peptide content, but the main liver drainage and brain-gut interaction have not been linked. The author took the correlation between liver liver govers regulating and brain-gut interaction as the starting point, explored the mechanism of Tongxie Yaofang in treating IBS-D based on brain-gut interaction disorder, and explained the correlation between the three. Based on the research literature of Tongxie Yaofang in the past 5 years and the interaction between Tongxie Yaofang and brain-gut interaction, the author explored the effect of Tongxie Yaofang in treating IBS-D by affecting the brain-gut axis and brain-gut peptides.

Effect of Changji'an Prescription on Intestinal Permeability of IBS-D Rats / 中国实验方剂学杂志

Objective:To observe the effect of Changji'an prescription on intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats and explore its mechanism for treatment of IBS-D. Method:Male SD neonatal rats were randomly divided into five groups:normal group, model group, pinaverium bromide group(0.018 g·kg-1), high-dose(33.48 g·kg-1) and low-dose (16.74 g·kg-1)Changji'an prescription groups. Except for the normal group, the IBS-D model was established by the combination of maternal and infant separation+acetic acid stimulation+restraint stress. After drug treatment, the ultrastructure of rat intestinal mucosa was observed by using transmission electron microscopy and the plasma D-lactate level was detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of tight junction proteins Occludin and Claudin-1 were detected by Western blot. The mRNA expression levels of Occludin,Claudin-1 and zonula occluden(ZO)-1 were detected by real time polymerase chain reaction (Real-time PCR). Result:As compared with the normal group, the intestinal mucosal epithelial cells were damaged in IBS-D model group, and the microvilli arrangement was sparse and tight junction was widened, and some were not obvious,and the plasma D-lactate level in IBS-D rats was increased significantly (PPD-lactate level in pinaverium bromide group and high-dose Changji'an prescription group was significantly decreased (PD-lactate level in the low-dose group Changji'an prescription group had a tendency to decrease with no statistical difference. The mRNA and protein expression levels of Occludin and Claudin-1 and the mRNA expression of ZO-1 in the colon of rats in each administration group were higher than those in the model group (PConclusion:The therapeutic effect of Changji'an prescription on IBS-D may be achieved by improving the intestinal permeability.

A randomised double blind placebo controlled trial to assess the efficacy and tolerability of short course of ornidazole in diarrhoea predominant irritable bowel syndrome

Background: Irritable bowel syndrome is a common disorder affecting the general population. At present the treatment is mainly symptomatic as the pathophysiology is not clear. Abnormal flora especially small bowel bacterial over growth is considered as one of the causes. A short course of ornidazole is compared with placebo to assess its efficacy and tolerability in diarrhoea predominant irritable bowel syndrome.Methods: This was a randomised double-blind placebo controlled trial done in the Departments of Gastroenterology and Pharmacology at Government Medical College, Calicut. Patients were randomly assigned to two groups to receive either ornidazole or Placebo. The baseline symptoms were recorded and graded to get a global symptom score. Patients assigned to ornidazole group received 500mg twice daily orally for 5 days and the control group received identical looking placebo tablets. The patients were reassessed every week for four weeks. The patients subjective global assessment of relief and global symptom score was recorded. Statistical analysis was done using Wilcoxon signed Rank test and Mann Whitney U test.Results: This study was done in twenty patients with a mean age of 30 with comparable baseline characteristics and symptom scores (p=0.969). Ornidazole produced a highly significant reduction in the global symptom score (p<0.001) compared to placebo. It was maintained through the four weeks follow up. No serious adverse effects were reported. Two patients reported burning sensation in the stomach which was self limited.Conclusions: Ornidazole is efficacious than placebo in controlling the symptoms of diarrhoea predominant irritable bowel syndrome and is well tolerated.

Abnormal SCF-C-kit system in IBS-D rat and the correlation between SCF-C-kit system and immune function / 中国药理学通报

Aim To explore the change of stem cell factor-C-kit (SCF-C-kit) system in irritable bowel syn-drome with diarrhea ( IBS-D) and the correlation be-tween SCF-C-kit system and immune dysfunction . Methods Twelve neonatal rats were divided into nor-mal group and model group with six rats in each group . IBS-D rat model was established through three-factor method ( mother-son separation , acetic acid stimulation and constraint ) . Immunohistochemistry was used to observe in situ protein expressions of SCF and C-kit. qPCR was used for mRNA expressions of SCF and C-kit.Correlation between SCF-C-kit system and spleen coefficients , thymus coefficients , TNF-α, IL-8 , IL-10 was analyzed by statistics .Results Compared with normal group , positive rates of SCF and C-kit protein in model group both decreased , and so did mRNA ex-pression .Expression of SCF was negatively correlative with spleen coefficient , TNF-αexpression and IL-8 ex-pression , while positively correlative with IL-10 expres-sion.Expression of C-kit was negatively correlated with thymus coefficient , spleen coefficient and TNF-α. Conclusion SCF-C-kit system of IBS-D is abnormal, which may be related with immune dysfunction .

Research Progress in Animal Models of IBS-D Disease Combined with Liver Stagnation and Spleen Deficiency / 中国中医药信息杂志

At present, TCM treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) is based on the combination of disease differentiation and syndrome differentiation. Therefore, the establishment of IBS-D of liver stagnation and spleen deficiency syndrome combined with animal model as a combination of traditional Chinese and Western medicine innovation theory has become increasingly concerned about, and gradually become a new direction for the development of TCM experimental animal model. This article reviewed the research progress in IBS-D liver and spleen deficiency syndrome in recent years, discussed the establishment of IBS-D liver stagnation and spleen deficiency animal model and research ideas for the treatment of IBS-D, and provided references for mechanism research of TCM treatment for IBS-D and research and development of new medicine.

Effect of Acupuncture plus Medication on Serum 5-HT, CGRP and ET in IBS-D / 上海针灸杂志

Objective To observe the efficacy of acupuncture plus medication in treating diarrhea-irritable bowel syndrome (IBS-D) due to liver depression and spleen deficiency, and its effect on serum 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP) and endothelin (ET). Method Sixty IBS-D (liver depression and spleen deficiency) were recruited and randomized into an observation group and a control group, 30 cases each. Patients in the observation group were intervened by acupuncture plus modified Bai Zhu Shao Yao powder, while the control group was intervened by acupuncture alone. The total effective rate, change of syndrome score of traditional Chinese medicine (TCM) and diarrhea-irritable bowel syndrome quality of life scale (IBS-QOL), as well as the levels of serum 5-HT, CGRP and ET, were observed. Result The total effective rate was 83.3% in the observation group, significantlyhigher than 63.3% in the control group (P0.05). The global and component TCM symptoms scores and IBS-QOL dropped significantly in both groups after the intervention (P0.05) before the treatment. The levels of 5-HT, CGRP and ET decreased significantly after the treatment in both groups (P<0.05); after the intervention, the levels of 5-HT, CGRP and ET in the observation group were significantly lower than those in the control group (P<0.05). Conclusion Acupuncture plus medication can effectively mitigate the symptoms in IBS-D (liver depression and spleen deficiency) and enhance the quality of life, which is possibly achieved by down-regulating the serum 5-HT, CGRP and ET levels.

Study on Relationship between the Main Symptoms Distribution and Different Factors of 360 Cases of IBS-D / 中国中医药信息杂志

Objective To study the epidemiological characteristics of diarrhea-predominant irritable bowel syndrome (IBS-D) as well as the relationship between the main syndromes and different factors. Method The relevant information of patients were collected by clinical epidemiological method and the relationship between the main characteristics of the IBS-D syndromes and different factors was explored with the major syndromes as the key link. Result Most of the cases aged 30～49 years old. Special hobbies of patients followed by drinking, smoking, addicting spicy, addicting coffee and so on. Poor emotion, mental stress and diet were the main inducements. Liver stagnation and spleen deficiency has the highest percentage (44.7%). The distribution of syndromes in different ages, different genders, different occupations and different education had no significant difference. Conclusion The number of IBS-D hospital visiting-patients is lower than the actual number of illness people. Mental factors are important internal factors, and dietary factors may be an important external factor. Different factors have no effect on the distribution of syndromes.