Luteolin ameliorates loperamide-induced functional constipation in mice

Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

Effect of closure of anterior abdominal wall layers on early postoperative findings at cesarean section: A prospective cross-sectional study

Abstract Objective To investigate the effect of closure types of the anterior abdominal wall layers in cesarean section (CS) surgery on early postoperative findings. Methods The present study was designed as a prospective cross-sectional study and was conducted at a university hospital between October 2018 and February 2019. A total of 180 patients who underwent CS for various reasons were enrolled in the study. Each patient was randomly assigned to one of three groups: Both parietal peritoneum and rectus abdominis muscle left open (group 1), parietal peritoneum closure only (group 2), and closure of the parietal peritoneum and reapproximation of rectus muscle (group 3). All patients were compared in terms of postoperative pain scores (while lying down and duringmobilization), analgesia requirement, and return of bowel motility. Results The postoperative pain scores were similar at the 2nd, 6th, 12th, and 18th hours while lying down. During mobilization, the postoperative pain scores at 6 and 12 hours were significantly higher in group 2 than in group 3. Diclofenac use was significantly higher in patients in group 1 than in those in group 2. Meperidine requirements were similar among the groups. There was no difference between the groups' first flatus and stool passage times. Conclusion In the group with only parietal peritoneum closure, the pain scores at the 6th and 12th hours were higher. Rectus abdominismuscle reapproximations were found not to increase the pain score. The closure of the anterior abdominal wall had no effect on the return of bowel motility.

Papel del sistema cannabinoide endógeno en el intestino / Role of the endogenous cannabinoid system in the gut / Papel do sistema canabinoide endógeno no intestino

RESUMEN El sistema cannabinoide endógeno es un nuevo sistema de comunicación intercelular que constituye una pieza crucial en la regulación de la función intestinal. Se realizó una revisión bibliográfica con el objetivo de describir cómo el sistema cannabinoide endógeno modula la función intestinal. Se consultaron un total de 31 referencias bibliográficas entre libros, revistas, tesis doctorales y artículos en internet. Se encontró que los endocannabinoides son inmunomoduladores a nivel intestinal, que el sistema cannabinoide endógeno regula la composición de la microbiota intestinal y esta a su vez determina la concentración de los endocannabinoides, además tanto la secreción como la motilidad intestinal disminuyen por estimulación del sistema cannabinoide endógeno. Los receptores de cannabinoides, los endocannabinoides anandamida y 2-araquidonoilglirerol y las proteínas responsables de su síntesis y degradación están ampliamente distribuidos en el intestino en condiciones fisiológicas, aumentando su expresión en la enfermedad inflamatoria intestinal lo que le permite regular la función intestinal en ambas condiciones. El sistema cannabinoide endógeno tiene un enorme potencial terapéutico en la enfermedad inflamatoria intestinal debido a los efectos inmunosupresores, antiinflamatorios y analgésicos que posee.

ABSTRACT The endogenous cannabinoid system is a new intercellular communication system that constitutes a crucial piece in the regulation of intestinal function. A bibliographic review was carried out in order to describe how the endogenous cannabinoid system modulates intestinal function. A total of 31 bibliographic references were consulted between books, magazines, doctoral theses and articles on the internet. It was found that endocannabinoids are immunomodulatory at the intestinal level, that the endogenous cannabinoid system regulates the composition of the intestinal microbiota and this in turn determines the concentration of endocannabinoids, in addition both secretion and intestinal motility decrease by stimulation of the endogenous cannabinoid system. The cannabinoid receptors, the endocannabinoids anandamide and 2-arachidonoylglirerol, and the proteins responsible for their synthesis and degradation are widely distributed in the intestine under physiological conditions, increasing their expression in inflammatory bowel disease, which allows it to regulate intestinal function in both conditions. The endogenous cannabinoid system has enormous therapeutic potential in inflammatory bowel disease due to its immunosuppressive, anti-inflammatory and analgesic effects.

RESUMO O sistema canabinoide endógeno é umnovo sistema de comunicação intercelular que constitui uma peça crucial na regulação da função intestinal. Foi realizada uma revisão bibliográfica para descrever como o sistema canabinoide endógeno modula a função intestinal. Foram consultadas 31referências bibliográficas entre livros, revistas, teses de doutorado e artigosna internet. Verificou-se que os endocanabinoides são imunomoduladores em nível intestinal, que o sistema canabinoide endógeno regula a composição da microbiota intestinal e esta, por sua vez, determina a concentração de endocanabinoides, além da diminuição da secreção e da motilidade intestinal pela estimulação do sistema canabinoide endógeno. Os receptores canabinoides, os endocanabinoides anandamida e 2-araquidonoilglirerol e as proteínas responsáveis ​​por sua síntese e degradação estão amplamente distribuídos no intestino em condições fisiológicas, aumentando sua expressão em doenças inflamatórias intestinais que permitem regular a função intestinal em ambas as condições. O sistema canabinoide endógeno apresenta enorme potencial terapêutico na doença inflamatória intestinal devido aos seus efeitos imunossupressores, antiinflamatórios e analgésicos.

Effect of Dendrobium officinale on Yin deficiency constipation induced by warm-drying medicine in mice / 中国中药杂志

Dendrobium officinale is a sacred product for nourishing Yin and has a clear "thick gastrointestinal" effect. Modern pharmacological studies had found that it could improve gastrointestinal function. This study observed the improvement effect of D. officinale on constipation model mice with Yin deficiency caused by warm-drying medicine. It provided experimental basis for the treatment of Yin deficiency constipation. The male and female ICR mice were randomly divided into normal group, model group, D. officinale high, medium and low dose groups(0.6, 0.4, 0.2 g·kg~(-1)), and phenolphthalein tablets group. The model mice of Yin deficiency constipation were established by gavage with warm-drying medicine. The overall state and body temperature of the mice were observed and recorded. The number of feces, feces weight, fecal moisture content and intestinal propulsion were measured. The morphological damage of colon tissue was observed by hematoxylin-eosin(HE) staining. The expression of inducible nitric oxide synthase(iNOS) in the colon was detected by Western blot and immunohistochemical method. The expression of iNOS mRNA in the colon was detected by Real-time fluorescence quantitative PCR, and the serum cyclic guanosine phosphate(cGMP) level was detected the enzyme-linked immunosorbent assay(ELISA). The results showed that D. candidum could reduce the body temperature of mice with Yin deficiency constipation, increase the number of feces, wet feces, dry feces and intestinal propulsion ability, reduce the expression of iNOS protein and mRNA in the colon, and reduce the content of cGMP in the serum. It showed that D. candidum could improve the symptoms of Yin deficiency constipation mice caused by warm-drying medicine, and the mechanism may be related to reducing the expression of iNOS in the colon and increasing intestinal motility.

Study on the mechanism of Dahuangfuzi decoction in improving intestinal motility disorder of rats with severe acute pancreatitis / 中华急诊医学杂志

Objective:To explore the mechanism of Dahuangfuzi decoction on intestinal motility disorder by observing its effect on serum motilin, Cajal interstitial cells and motilin receptor in rats with severe acute pancreatitis (SAP).Methods:Eighteen clean male Sprague-Dawley rats were randomly divided into the control group, SAP group and Dahuangfuzi group ( n=6 each group). The SAP rat model was prepared by retrogradely injected 4% sodium taurocholate into cholangiopancreatic duct. The rats in the SAP group were given 2 mL normal saline (37℃) enema at 12 and 24 h after operation. The rats in the Dahuangfuzi group was given 2 mL Dahuangfuzi decoction (37℃) enema at 12 and 24 h respectively. For the control group, the pancreas was exposed in the same way and then the abdomen was closed. Forty-eight h after operation, the abdominal aorta blood samples were taken for determination of serum endotoxin and amylase, and for detection of serum motilin by enzyme-linked immunosorbent assay (ELISA); the pathological changes of pancreas and ileum were observed by hematoxylin-eosin (HE) staining. The expression of c-kit and motilin receptor protein in ICC in ileum tissue was detected by immunohistochemistry. Results:Compared with the control group, the levels of serum endotoxin and amylase in the SAP group were significantly higher [(504.98±88.81) pg/mL vs. (17.76±5.01) pg/mL; (532.28±66.53) vs. (69.45±3.61) U/L, P<0.05], while the levels of serum motilin were significantly lower [(195.4±6.7) ng/L vs. (301±8.10) ng/L, P<0.05], and the scores of c-kit and motilin receptor protein were decreased ( P<0.05); compared with the SAP group, the levels of serum endotoxin and amylase in the Dahuangfuzi group were significantly reduced [(189.9±38.23) pg/mL vs. (504.98±88.81) pg/mL; (294.23±25.66) vs. (532.28±66.53) U/L, P<0.05], while the levels of serum motilin were significantly increased [(264.2±8.3) ng/L vs. (195.4±6.7) ng/L, P<0.05], and the scores of c-kit and motilin receptor protein were increased ( P<0.05). Conclusions:Dahuangfuzi decoction can improve the intestinal motility of SAP rats by promoting the secretion of motilin, increasing the activity of ICC cells and the expression of motilin receptor.

Effect of Huatan Tongluo Decoction on Gut-Brain Axis in Rats with Cerebral Ischemia/Reperfusion / 中国实验方剂学杂志

Objective:To explore the effects of Huatan Tongluo Decoction （HTTLD） on the morphology and function of brain tissues and intestine in rats with cerebral ischemia/reperfusion based on the gut-brain axis. Method:Sixty SPF male rats were randomly divided into a sham operation group， a model group， high- （28.66 g·kg^-1）， medium- （14.33 g·kg^-1）， and low-dose （7.16 g·kg^-1） HTTLD groups， and an edaravone （4 g·kg^-1）+<italic>Clostridium butyricum</italic> （5.0×10⁸ cfu·mL^-1） group. The model was established by focal cerebral ischemia/reperfusion in rats. The drugs were administered by gavage. The brain tissue injury was determined by neurological deficit score and 2，3，5-triphenyl tetrazolium chloride （TTC） staining. The effect of cerebral ischemia/reperfusion on intestinal motility was assessed by the propulsion rate of small intestine. The intestinal mucosal cell damage was evaluated by the pathomorphological examination of the duodenal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of <italic>D</italic>-lactate （<italic>D</italic>-LAC）， diamine oxidase （DAO）， and bacterial endotoxin （lipopolysaccharide， LPS） in serum. Western blot was used to detect the expression of Occludin， Claudin-5， and zonula occludens 1 （ZO-1） in the duodenum. Result:After cerebral ischemia/reperfusion， rats developed neurological deficit symptoms. The neurological deficit score in the model group was higher than that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the high- and medium-dose HTTLD groups could relieve the symptoms of neurological deficits and lower neurological deficit scores （<italic>P<</italic>0.01）. The results of TTC staining showed that the model group presented obvious infarcts in brain tissues compared with the sham operation group （<italic>P<</italic>0.01）. The cerebral infarction volumes of HTTLD groups were reduced compared with that in the model group （<italic>P<</italic>0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. Furthermore， the propulsion rate of small intestine in the model group was significantly reduced compared with that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， HTTLD groups could increase propulsion rates of small intestine （<italic>P<</italic>0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. After cerebral ischemia/reperfusion， obvious duodenal mucosal damage could be observed， which was relieved after the administration of HTTLD. Western blot results showed that the protein expression of ZO-1， Occludin， and Claudin-5 in the model group was reduced compared with that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the HTTLD groups could up-regulate the expression of ZO-1， Occludin， and Claudin-5 to varying degrees （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， especially the high-dose HTTLD group. ELISA showed that the serum <italic>D</italic>-LAC， DAO， and LPS of the model group were elevated compared with those in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the HTTLD groups showed reduced <italic>D</italic>-LAC and DAO （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and the medium- and high-dose HTTLD groups showed reduced LPS （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， especially the high-dose HTTLD group. Conclusion:After cerebral ischemia/reperfusion， the rats showed damaged brain tissues， neurological dysfunction， intestinal mucosal injury， weakened intestinal motility， and destroyed the intestinal mucosal barrier. HTTLD can protect against brain-gut axis injury after cerebral ischemia/reperfusion by reducing the damage on brain tissues and gastrointestinal mucosa， relieving the symptoms of neurological deficits， promoting gastrointestinal motility， improving intestinal barrier function， and reducing the release of intestinal bacterial metabolites or poisons.

The effect of caffeine ingestion in prevention of post-operative ileus after caesarean section: a randomized controlled trial

Background: Caesarian section (CS) has become more prevalent than the vaginal delivery in Egypt. Many complications could occur after an abdominal surgery. One of the commonest but yet serious complications is the postoperative ileus that can possibly be prevented by caffeine ingestion. The aim of the study is to assess the value of caffeine ingestion in promoting intestinal motility and prevention of postoperative ileus after CS.Methods: This is a randomized controlled trial that was conducted on 560 cases who were recruited from emergency unit and inpatient wards in Ain Shams University maternity hospital. The patients were divided into two groups where the intervention group received caffeinated coffee while the other group received decaffeinated coffee.Results: There was statistically significant difference between the two groups regarding the bowel function after CS (p <0.05). The intervention group had improved intestinal functions after the CS. Patients from the intervention group had audible intestinal sound sooner than the control group. In addition, they passed flatus and were able to tolerate food in less time.Conclusions: Consuming caffeinated coffee after CS contributes significantly to faster restoration of intestinal function. Coffee is a popular drink and can be used to decrease the incidence of postoperative ileus-related complications.

Antibacterial and antidiarrheal activity of Simarouba amara (Aubl.) bark

The present study was conducted to determine the nutritional elements in Simarouba amara (Aubl.) bark aqueousextract (SAAE) by inductively coupled plasma optical emission spectrometry (ICP-OES) and the in vitroantibacterial activity against pathogens enterotoxigenic Escherichia coli, Salmonella typhi, Staphylococcous aureus,Klebsiella pneumoniae, and Pseudomonas aeruginosa by agar well diffusion, minimum inhibitory, and bactericidalconcentration. Then, antidiarrheal effect was studied on castor oil-induced diarrhea in mice model. Recorded Mg > Fe> Cu > Zn elements in SAAE invariably found to be effective against Gram-positive and Gram-negative pathogens.Effective concentration of bark showed the zone of inhibition against enterotoxigenic E. coli (200 mg/ml), S. typhiand S. aureus (300 mg/ml), and P. aeruginosa and K. pneumonia (100 mg/ml). The standard ratio between minimuminhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was meticulously recorded “one”against all pathogens, which confirms the bactericidal property. Results in mice model prominently showed that SAAEsignificantly (p < 0.05) reduced the frequency and number of diarrheal episodes, intestinal fluid accumulation, andintestinal transit time in dose-dependent manner. Inordinate delay in charcoal movement in the intestine positivelyconfirmed the antispasmodic effect by reducing propulsive movement. Confirmed findings in this study naturallysuggested that SAAE could be an effective antibacterial and antidiarrheal formulation.

Does gum chewing affect the timing of return of intestinal motility after elective cesarean section?

Background: The aim is to evaluate the effect of gum chewing on the return of intestinal motility after elective CS.Methods: Study period was from September 2017 to March 2018 at the Assiut Women Health University Hospital. The study was registered as a prospective cohort study (Clinicaltrial.gov   NCT03355378). Women planned for elective CS according to selection criteria randomized to two groups: Group 1: included 100 patients who received intraoperative and postoperative non-sugary gum chewing as 15 minutes every 2 hours post-operatively for 6 hours with regular care and Group 2: included 100 patients who received regular care without gum chewing.Results: No statistically significant difference regarding the baseline criteria of both groups. There was a statistically significant lower systolic and diastolic blood pressure in gum chewing group. Hospital stay of gum chewing group was 7.33±0.73 hours versus in non-gum chewing group 20.28 ± 9.92 (p=0.000). Passage of flatus of gum chewing group was 8.54±0.98 hours versus in non-gum chewing group 13.22 ± 3.75 (P= 0.000).Conclusions: Gum chewing during elective CS improves gut motility in a safe way resulting in early passage of flatus, less hospital stay, and minimal pain score less cost on hospitals.

Effect of intestinal flora on expression of acid-sensitive ion channel 3 in rats and their regulation in intestinal motility in children with functional constipation / 中华实用儿科临床杂志

Objective@#To investigate the effect of intestinal flora in children with functional constipation (FC) on expression of acid-sensitive Ion channel 3(ASIC3) in rats and their regulation in intestinal motility.@*Methods@#Faeces of FC children identified according to RomeⅣ criteria and healthy children from the First Affiliated Hospital of Anhui Medical University from December 2017 to June 2018 were collected, and then made into fecal microbiota solution.A pseudo - sterile rat model was established, according to the random number table method, and the rats were randomly divided into the treatment group and the control group, with 12 rats in each group, then the treatment group was given fecal microbiota solution of the children with FC and the control group was given fecal microbiota solution of the healthy children.The visceral sensitivity and intestinal propulsion rate of rats were determined by means of abdominal withdrawal reflex (AWR), while the intestinal microorganism of rats and children with FC were determined by 16SrDNA high-throughput sequencing, and the expressions of ASIC3 of intestinal in mRNA and protein were determined by adopting fluorescence quantitative PCR and Western blot.@*Results@#The species and quantity of intestinal flora of the children with FC and rats implanted with FC faecal bacteria were reduced(all P<0.05), and firmicutes and bacteroidetes were the main bacteria; compared to the control group, the small intestine propulsion rate(52% vs.74%) and visceral sensitivity(78 mmHg vs.63 mmHg) of the treated group were significantly decreased compared with those in the control group (all P<0.05); the mRNA (0.003 1±0.000 8 vs.0.012 4±0.002 5) and protein levels of ASIC3 (0.013 2±0.001 9 vs.0.072 1±0.008 7) in the small intestine were down-regulated significantly(all P<0.05); and the mRNA (0.002 8±0.000 7 vs.0.009 4±0.001 1) and protein levels of ASIC3(0.038 2±0.004 5 vs.0.089 7±0.009 4) in the colon were down-regulated significantly(all P<0.05).@*Conclusions@#Children with FC have intestinal flora disorder, and intestinal flora of FC children may affect intestinal motility by down-regulating the expression of intestinal ASIC3 in rats.

Effects of dipyrone on the digestive tract

Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.

Regulation of Intracellular Calcium by Endoplasmic Reticulum Proteins in Small Intestinal Interstitial Cells of Cajal

BACKGROUND/AIMS: We investigated the role of representative endoplasmic reticulum proteins, stromal interaction molecule 1 (STIM1), and store-operated calcium entry-associated regulatory factor (SARAF) in pacemaker activity in cultured interstitial cells of Cajal (ICCs) isolated from mouse small intestine. METHODS: The whole-cell patch clamp technique applied for intracellular calcium ions ([Ca²+]i) analysis with STIM1 or SARAF overexpressed cultured ICCs from mouse small intestine. RESULTS: In the current-clamping mode, cultured ICCs displayed spontaneous pacemaker potentials. External carbachol exposure produced tonic membrane depolarization in the current-clamp mode, which recovered within a few seconds into normal pacemaker potentials. In STIM1-overexpressing cultured ICCs pacemaker potential frequency was increased, and in SARAF-overexpressing ICCs pacemaker potential frequency was strongly inhibited. The application of gadolinium (a non-selective cation channel inhibitor) or a Ca2+-free solution to understand Orai channel involvement abolished the generation of pacemaker potentials. When recording intracellular Ca²+ concentration with Fluo 3-AM, STIM1-overexpressing ICCs showed an increased number of spontaneous intracellular Ca²+ oscillations. However, SARAF-overexpressing ICCs showed fewer spontaneous intracellular Ca2+ oscillations. CONCLUSION: Endoplasmic reticulum proteins modulated the frequency of pacemaker activity in ICCs, and levels of STIM1 and SARAF may determine slow wave patterns in the gastrointestinal tract.

LAXATIVE EFFECT OF RHEUM UNDULATUM L. EXTRACT ON LOPERAMIDE INDUCED CONSTIPATION IN WISTAR RATS / Монголын эм зүй, эм судлал

Introduction: Constipation is highly prevalent, often chronic gastrointestinal disorder that affects adults. The treatment with classic drugs did not cut, in one hand with the inadequate relief of bloating and other symptoms, and with the luck of efficacy in relieving constipation. Therefore, the search for novel safe laxative drugs seems, inevitable. Rheum undulatum L. was traditionally used in constipation, thus we have attempted to evaluate the laxative effect of Rheum undulatum L. Purpose: The laxative effect of Rheum undulatum L. was evaluated against loperamide induced constipated rats. Methodology: Fifteen male normal rats were used in this study. Fifteen male constipated wistar albino rats weighing 180-250 g were also used for the study and randomized into three groups (n=5) in each of the experiments. Constipated control group rats oral administrated distilled water. Constipated rats (treatment groups) were treated with 4.1 mg/kg dose body weight /day of the preparation for one day and also Laxing a standard drug was used for the reference group. The fecal weight, the fecal humidity laxative activity were monitored in experimental rats.Results: Constipation was successfully induced in the rats by loperamide as seen in the elevated fecal properties compared to the control rats. The Rheum undulatum L. compounds preparation administered orally produced significant laxative activity and reduced loperamide induced constipation in dose dependent manner as seen in the increase of fecal output. The same doses of the Rheum undulatum L. compounds preparation produced a significant increase (P<0.05) fecal weight, the faeces humidity. The effect of the compounds preparation compares favourably well with Laxing, a standard laxative drug. Conclusion: The results of this study justify the use of Rheum undulatum L. compounds preparation as a laxative in traditional medicine. The produced significantly increase in fecal output of rats and the stimulation of gastrointestinal motility. Keywords: Laxative, gastro intestinal motility, loperamide, constipated

Laxative effect of Rheum undulatum L. Extract on loperamide induced constipation in wistar rats / Монголын эм зүй, эм судлал

Introduction@#Constipation is highly prevalent, often chronic gastrointestinal disorder that affects adults. The treatment with classic drugs did not cut, in one hand with the inadequate relief of bloating and other symptoms, and with the luck of efficacy in relieving constipation. Therefore, the search for novel safe laxative drugs seems, inevitable. Rheum undulatum L. was traditionally used in constipation, thus we have attempted to evaluate the laxative effect of Rheum undulatum L.@*Purpose@#The laxative effect of Rheum undulatum L. was evaluated against loperamide induced constipated rats.@*Methodology@#Fifteen male normal rats were used in this study. Fifteen male constipated wistar albino rats weighing 180-250 g were also used for the study and randomized into three groups (n=5) in each of the experiments. Constipated control group rats oral administrated distilled water. Constipated rats (treatment groups) were treated with 4.1 mg/kg dose body weight /day of the preparation for one day and also Laxing a standard drug was used for the reference group. The fecal weight, the fecal humidity laxative activity were monitored in experimental rats.@*Results@#Constipation was successfully induced in the rats by loperamide as seen in the elevated fecal properties compared to the control rats. The Rheum undulatum L. compounds preparation administered orally produced significant laxative activity and reduced loperamide induced constipation in dose dependent manner as seen in the increase of fecal output. The same doses of the Rheum undulatum L. compounds preparation produced a significant increase (P<0.05) fecal weight, the faeces humidity. The effect of the compounds preparation compares favourably well with Laxing, a standard laxative drug. @*Conclusion@#The results of this study justify the use of Rheum undulatum L. compounds preparation as a laxative in traditional medicine. The produced significantly increase in fecal output of rats and the stimulation of gastrointestinal motility.

Advance of the improvement effect of dietary fiber on intestinal motility disorders / 肠外与肠内营养

Intestinal motility disorders,one of the common complications of critically ill patients,can be caused by a variety of diseases.It was reported that intestinal motility disorders could be improved by modulating the micro-ecological environment in the distal digestive cavity and by reducing the bacterial toxins,and thereby it provides a new reference strategy for the treatment of intestinal motility disorders.Dictary fiber has physiological functions such as accelerating colonic transition,regulating the intestinal microflora and protecting the intestinal mucosal barrier.Clinically,dietary fiber is used as an adjuvant therapy of intestinal motility disorders widely in critical illness,inflammatory bowel disease and diabetes.In order to explore the relationship between the application of dietary fiber and the improvement of intestinal motility disorders,we retrieved the Chinese and English databases and summarized sone recent literatures for providing new ideas for the prevention and treatment of intestinal motility disorders.

Effects of pelvic nerves denervation on the expression of transit receptor potential vanilloid 1 in distal colonic mucosa of rats / 中华消化外科杂志

Objective To explore the effects of pelvic nerves denervation (PND) on the expression of transit potential receptor vanilloid 1 (TRPV1) in distal colonic mucosa of rats.Methods The experimental study was conducted.One hundred and eight adult male rats were randomly divided into the control group,sham operation group and PND group:(1) 36 rats in the control group remained untreated and were fed regularly;(2) 36 in the sham operation group received open exclusion for 15 minutes,and then sew up the incision;(3) 36 in the PND group received laparotomy with pelvic nerve transection before abdominal closure.The expression of TRPV1 protein in distal colonic mucosa was respectively detected by Western blot at postoperative day 1,3 and 7.Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the mRNA level of TRPV1 in the distal colonic mucosa.Measurement data with normal distribution were represented as (x)±s.Repeated measurement data were analyzed by repeated measures ANOVA.Comparisons at the same time intervals among the 3 groups were analyzed using one-way ANOVA.Pairwise comparison was done by the independent samples t test.Results (1) The results of immunohistochemical staining:the average density of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 was respectively 0.180±0.016,0.179±0.015 and 0.183±0.026 in the control group,with no statistically significant difference (F=0.088,P＞0.05).The average density of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 was respectively 0.132±0.017,0.160±0.023 and 0.173±0.020 in the sham operation group,with a statistically significant difference (F=8.699,P＜0.05).The average density of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 was respectively 0.057± 0.009,0.122±0.016 and 0.180± 0.016 in the PND group,with a statistically significant difference (F =113.315,P ＜ 0.05).There were statistically significant differences in the average density of TRPV1 at postoperative day 1 and 3 among the 3 groups (F =108.960,15.218,P＜ 0.05),while significant differences were respectively detected between the control group and the sham operation group or the PND group at postoperative day 1 (t =5.025,15.979,P＜0.05),and a significant difference was also detected between the sham operation group and the PND group (t =9.590,P＜0.05).There was no statistically significant difference in the average density of TRPV1 between the control group and the sham operation group at postoperative day 3 (t =1.670,P＞0.05),while significant differences were respectively detected between the control group and the PND group and between the sham operation group and the PND group (t=6.543,3.361,P＜0.05).There was no statistically significant difference in the average density of TRPV1 at postoperative day 7 among the 3 groups (F=0.518,P＞0.05).(2) The results of Western blot:the relative expressions of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 were respectively 1.02±0.13,1.00±0.15 and 1.00±0.10 in the control group,with no statistically significant difference (F=0.084,P＞0.05).The relative expressions of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 were respectively 0.51±0.13,0.93±0.14 and 1.01±0.16 in the sham operation group,with a statistically significant difference (F =20.930,P＜0.05).The relative expressions of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 were respectively 0.30±0.10,0.70±0.10 and 1.07±0.16 in the PND group,with a statistically significant difference (F=61.441,P＜0.05).There were statistically significant differences in the relative expressions of TRPV1 at postoperative day 1 and 3 among the 3 group (F=58.014,8.841,P＜0.05),while significant differences were respectively detected between the control group and the sham operation group or the PND group at postoperative day 1 (t =6.677,11.145,P＜0.05),and significant difference was also detected between the sham operation group and the PND group (t =3.287,P＜ 0.05).There was no statistically significant difference in the relative expressions of TRPV1 between the control group and the sham operation group at postoperative day 3 (t =0.798,P＞0.05),while significant differences were respectively detected between the control group and the PND group and between the sham operation group and the PND group (t=4.127,3.398,P＜0.05).There was no statistically significant difference in the relative expressions of TRPV1 at postoperative day 7 among the 3 group (F=0.428,P＞0.05).(3) The results of RTqPCR:the mRNA levels of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 were respectively 1.00±0.15,1.10±0.21 and 1.09±0.18 in the control group,with no statistically significant difference (F=0.489,P＞0.05).The mRNA levels of TRPV1 in distal colonic mueosa at postoperative day 1,3 and 7 were respectively 0.58±0.12,0.99±0.19 and 1.13±0.23 in the shan operation group,with a statistically significant difference (F=13.964,P＜0.05).The mRNA levels of TRPV1 in distal colonic mucosa at postoperative day 1,3 and 7 were respectively 0.31±0.10,0.67±0.12 and 1.09±0.19 in the PND group,with a statistically significant difference (F=44.642,P＜0.05).There were statistically significant differences in the mRNA levels of TRPV1 at postoperative day 1 and 3 among the 3 group (F=44.653,9.700,P＜0.05),while significant differences were respectively detected between the control group and the sham operation group or the PND group at postoperative day 1 (t=5.233,9.264,P＜0.05),and significant difference was also detected between the sham operation group and the PND group (t=4.127,P＜0.05).There was no significant difference in the mRNA levels of TRPV1 between the control group and the sham operation group at postoperative day 3 (t =0.995,P＞0.05),while significant differences were respectively detected between the control group and the PND group and between the sham operation group and the PND group (t =4.411,3.505,P＜0.05).There was no statistically significant difference in the mRNA levels of TRPV1 at postoperative day 7 among the 3 group (F=0.099,P＞0.05).Conclusion The expression of TRPV 1 in distal colonic mucosa of rats is significantly down-regulated after pelvic nerves denervation,however,it is gradually recovered with passage of time,which is consistent with the trend of gradual recovery of colonic transit function after pelvic nerve injury.

Efecto del extracto acuoso de Piper elongatum Vahl. (matico) sobre la motilidad intestinal en ratones / Effect of aqueous extract from Piper elongatum Vahl (matico) on the intestinal motility in mice

Objetivo: evaluar el efecto del extracto acuoso de Piper elongatum Vahl. (matico) sobre la motilidad intestinal en ratones BALB/c. Métodos: estudio experimental. Se empleó el método del carbón activado. Los grupos fueron: Grupo 1 control negativo con NaCl 9.0 por ciento, Grupo 2 control positivo con loperamida 10 mg/Kg, grupos tratamiento de la planta a dosis de 125 mg/Kg (Grupo3), 250 mg/Kg (Grupo4) y 500 mg/Kg (Grupo5). Se utilizaron las pruebas estadísticas de ShapiroWilk, ANOVA y Bonferroni; se consideró p<0,05 como significativo e intervalo de confianza 95 por ciento. Resultados: el porcentaje del intestino recorrido por el carbón activado fue de 69,4±4,5; 24,9±3,0; 75,3±4,3; 71,1±4,5; 56,4±2,7 y 59,4±3,0 en los grupos del 1 al 5, respectivamente. La prueba post hoc Bonferroni no mostró diferencias entre el control negativo y los grupos tratamiento con Piper elongatum Vahl., mientras que sí existió diferencia entre el control positivo con los demás grupos y entre el grupo 3 y 5 (p<0,001). Conclusiones: el extracto acuoso de las hojas de Piper elongatum Vahl. no posee efecto sobre la motilidad intestinal a las dosis evaluadas, se requieren más estudios(AU)

Objective: to evaluate the effect of aqueous extract from Piper elongatum Vahl (matico) on the intestinal motility in BALB/c mice. Methods: experimental study that used activated carbon. The involved groups were: Group 1 with negative control with 9.0 percent NaCl; Group 2 positive control with loperamide 10mg/Kg, groups treated with the plant at doses of 125 mg/kg (Group3), 250 mg/kg (Group4) and 500 mg/Kg (Group5). ShapiroWilk, ANOVA and Bonferroni statistical tests were used; p<0.05 was considered as significant and 95 percent confidence interval. Results: the percentages of intestine explored with the active charcoal were 69,4±4,5; 24,9±3,0; 75,3±4,3; 71,1±4,5; 56,4±2,7 and 59,4±3,0 in groups 1 to 5 respectively. The ANOVA on this variable showed a p<0,001. The post hoc Bonferroni test showed no differences between the negative control and treatment groups with Piper elongatum Vahl whereas there was a difference between the positive control and the other groups and between the groups 3 and 5 (p<0.001). Conclusions: the aqueous extract from Piper elongatum Vahl has no effect on the intestinal motility at the evaluated doses, so further studies are needed(AU)

Olanzapine May Inhibit Colonic Motility Associated with the 5-HT Receptor and Myosin Light Chain Kinase

OBJECTIVE: To study whether the effects of olanzapine on gastrointestinal motility is related to the serotonin antagonism and myosin light chain kinase. METHODS: Male Sprague-Dawley rats were randomly divided into four groups. Olanzapine gavage was performed for each treatment group during the course of 30 continuous days, while the same volume of saline was given to the rats in the control group. Defecation of the rats was observed on days 7 and 30 after olanzapine gavage. The effects of olanzapine on contraction of colonic smooth muscles were observed in ex vivo experiments. A Western blot was used to evaluate expression levels of the serotonin transporter (SERT) and MLCK in colon segments of the rats. RESULTS: ResultsaaCompared to the control group, 5-160 µM of olanzapine could inhibit dose-dependently the contraction of colonic smooth muscle ex vivo experiments. The maximum smooth muscle contraction effects of 5-HT and acetylcholine significantly decreased after treatment with 40-160 µM of olanzapine. Constipation was found in the olanzapine-treated rats on day 7 and have sustained day 30 after gavage. Expression of MLCK in olanzapine-treated rats was significantly decreased, whereas the expression of SERT significantly increased on the day 7, then significantly decreased on the day 30 after olanzapine gavage. CONCLUSION: SERT and MLCK may involve in the inhibition of colonic contraction induced by olanzapine.

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model

OBJECTIVE@#To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model.@*METHODS@#Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.@*RESULTS@#Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05).@*CONCLUSIONS@#Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.

Effect of agarwood extracts produced by the whole-tree agarwood-inducing technique on gastrointestinal motility and gastric ulcer / 国际药学研究杂志

Objective To evaluate the gastrointestinal regulative effect of agarwood extracts produced by the whole-tree agar- wood-inducing technique (Agar-Wit agarwood) to make scientific basis for the Agar-Wit agarwood exploration and usage in clinic. Methods Intestinal propelling effect assay marked by carbon powder, and gastric empting effect assay marked by methyl orange were used to evaluate the gastrointestinal effects of Agar-Wit agarwood on mice by single or constant repeated intragastric (ig) administration of water extract and ethanol extract, and then the index of intestinal peristaltic rate and methyl orange relative residual rate were calculated. Gastrtic ulcer model was established under water stress to appraise their protective function on rat stomach and to obtain the gastric ulcer index and inhibitory rate. Results The Agar-Wit agarwood ethanol extract significantly improved intestinal peristalsis and gastric empting function by single or constant repeated ig administration at the dose of 150 mg/kg. The ethanol extract of commercial agarwood also had the similar effect at the dose of 450 mg/kg. But the water extract did not have significant effect. The gas ulcer assay results showed that the ethanol extract significantly inhibited gastric ulcer happening by single ig administration. Additionally,constant repeated ig administration of ethanol extract showed the consistent results and the gastric ulcer inhibitory rate was (73.1±5.6)% at the dose of 300 mg/kg. Conclusion The Agar-Wit agarwood ethanol extracts have significant intestinal peristaltic effect,gastric empting effect and gastric ulcer inhibitory function.