Fecal Wet Weight Research Articles

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice

ObjectiveAbnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions. MethodsForty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry. ResultsEA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01). ConclusionEA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation.Please cite this article as: Xu MM, Guo Y, Chen Y, Zhang W, Wang L, Li Y. Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice. J Integr Med. 2023; Epub ahead of print.

The effect of polydextrose on fecal bulk and bowel function in mildly constipated healthy adults: a double-blind, placebo controlled study

Background &amp; Aims. Polydextrose (PDX) (8-30g/day) has been reported to increase faecal bulk and consistency, leading to easier stool passage. However, studies on its effect on defaecation frequency and colonic transit time have provided mixed results, and most focused on either healthy or highly constipated adults, leaving the question on if and how PDX could also aid mildly constipated individuals partially unanswered.Methods. We investigated the effects of PDX consumption by healthy subjects experiencing one or more symptoms of mild constipation on faecal bulk, defaecation frequency, stool consistency, ease of stool passage, and total colonic transit time to further characterize and generate additional evidence regarding the potential beneficial effects of this fibre. 51 subjects participated in a 4-week, two-center, randomized, double-blind, placebo-controlled, parallel study testing a control (CON) and a PDX treatment (18 g/d included in biscuits and drink mixtures) (registered on clinicaltrials.gov with the identifier" NCT05309837").Results. Consumption of PDX resulted in 120.7 g and 25.7 g higher faecal wet and dry weight, respectively (p &lt; 0.05). Colonic transit time was ~4 h shorter in the PDX group: although this difference did not reach significance (p &gt; 0.05) as the study was underpowered to detect a statistical difference for this secondary outcome, this result still carries a physiological importance. Consumption of PDX was well-tolerated, with some PDX volunteers reporting more mild flatulence (p &lt; 0.05).Conclusions. All in all, our study adds new evidence on how a moderate (18g) daily intake of PDX could increase faecal bulking and potentially shorten colonic transit time, making this ingredient a good candidate to be used to formulate, and reformulate, foods and beverages by replacing caloric carbohydrates with reduced caloric content, enriching food items easily consumed to enhance fibre intake and support bowel function.

Using cereal to increase dietary fiber intake to the recommended level and the effect of fiber on bowel function in healthy persons consuming North American diets

Background:Dietary fiber intake remains low despite increasing evidence for its health benefits, including laxation. Objective:We aimed to assess the effects of increasing fiber intake on bowel habits and gastrointestinal tolerance in healthy persons consuming a typical Canadian or US diet. Design:Under a randomized crossover design, 23 free-living participants consumed a typical Canadian or US diet (35% fat, 12 g fiber/d) and received 25.0–28.7 g fiber/d from each of 5 breakfast cereals: All-Bran (AB), Bran Buds with Corn (BBC), Bran Buds with Psyllium (BBP), BBC with viscous fiber blend (VFB), or a low-fiber control for 3 wk, with each study arm separated by a washout of ≥1 wk. Seven-day stool collections and a symptom diary were obtained during the last week of each study arm. Results:All study cereals induced significant (P < 0.05) increases in fecal bulk from the control diet at 128 ± 38 g to 199 ± 56, 199 ± 57, 247 ± 87, and 197 ± 63 g with consumption of AB, BBC, BBP, and VFB, respectively; less intestinal transit time; and significantly (P < 0.05) greater bowel movement frequency. Despite the increased activity of the bowel, a positive level of comfort was maintained. BBP was more effective than other cereals in terms of increasing fecal wet weight (P < 0.05). Conclusion:Water-insoluble dietary fibers (ie, AB and BBC) and their mixtures with water-soluble fibers (ie, BBP and VFB) in the form of breakfast cereals (2.5 servings/d) proved to be a practical way of increasing fiber intake to recommended levels, while maintaining a good level of tolerance.

Nostoc sphaeroides Kütz Polysaccharide Improved Constipation and Promoted Intestinal Motility in Rats.

Natural products and medicinal foods have attracted more and more attention because of their potential prevention and inhibition effect on constipation. Nostoc sphaeroides Kütz Polysaccharide (NSKP) polysaccharide is a natural product rich in polysaccharides. This work attempted to prove the effects of aqueous extracts of NSKP on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. The results show that, in rats of the NSKP group, compared with the model group, the colon propulsion rate was improved, the time of the first grain of black stool was shortened, and the fecal wet weight was increased remarkably. The 5-HT levels were increased, but the VIP and NO levels were reduced dramatically. The number of interstitial cells of cajal (ICC) was increased by c-kit/SCF signal pathway, and the intestines were moisturized; then, constipation was relieved. It is interesting to note that NSKP appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with short bowel syndrome and colon in continuity: an open-label pilot study

ObjectivePatients with short bowel syndrome (SBS) and colon in continuity have better adaptation potential compared with patients with jejunostomy. Adaptation may involve enhanced postprandial secretion of the enteroendocrine hormones glucagon-like...

Toxicological evaluation of banana and milk combination as incompatible diet - An experimental exploration of Samyoga viruddha concept

BackgroundFood is the basic requirement and an essential part of all living beings which sustains life. A lot of emphasize has been given to food in the classics of Ayurveda and a detailed description of food which are both wholesome and unwholesome have been described. Viruddhahara (incompatible food) is a unique concept explained in Ayurveda which, in long run, may be harmful to the body. Objective(s)Intake of Kadaliphala (Musa paradisiaca. Linn, a variety of banana) and cow milk is an example of Samyoga Viruddha (incompatibility with reference to combination of things). This combination is routinely consumed by people. The present study was planned to evaluate the toxicological implication of their combination on wistar rats. Materials and methodsA subacute toxicity study was conducted on Wistar rats following the repeated dose 28-day oral toxicity study in rodents, 407 - OECD guidelines. Different haematological and biochemical parameters along with histopathology of important organs were carried out to assess the toxicological implication of the combination. ResultsRepeated administration of the combination of Kadaliphala (Banana) and cow milk showed statistically significant increase in SGOT & urea and statistically significant decrease in creatinine. Significant decrease was observed in the food intake, faecal wet weight and faecal water in the 7th day of study, food conversion ratio in the 14th day of study, in the food intake, faecal wet weight and faecal water in the 21st day of study and significant decrease in the food conversion ratio in the 28th day of study. In histopathological examination, the test drug administered group showed mild to moderate myocarditis in the sections from heart. In sections from liver of two rats of test group, diffused micro fatty changes were observed. In sections from spleen; mild to moderate increase in the white pulp portion was observed. ConclusionMarked variation in SGOT, urea and creatinine levels and alteration in sections of heart, liver and spleen are indicative of mild toxicological implications of the combination of banana and milk. Continuous intake of this incompatible combination may hence prove harmful to the body.

Effect of Bifidobacterium animalis subsp. lactis MN-Gup on constipation and the composition of gut microbiota.

Probiotics have been reported to be associated with the alleviation of constipation. The aim of this study was to detect and determine the effect of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) on the alleviation of constipation in BALB/c mice and humans, and to elucidate the mechanisms underlying its effect by measuring changes in the concentration of short-chain fatty acids and the composition of microbes in human faeces. BALB/c mice were given MN-Gup by gavage for 14 days. On the 8th day of this treatment, constipation was induced by the application of diphenoxylate via gavage. The results showed that MN-Gup significantly decreased the first black stool defecation time, and significantly increased black faecal wet weight, black faecal number and the gastric-intestinal transit rate (P<0.05), thereby relieving constipation. In humans, a randomised, double-blind, placebo-controlled trial was performed to investigate the effect of MN-Gup in adults with functional constipation. After 4 weeks of intervention with placebo or MN-Gup yogurt, constipation-related symptoms (including defecation frequency, stool consistency, straining and incomplete feeling during defecation) in the constipated subjects were significantly improved in the two groups, but not different between the groups at the end of the intervention. The concentration of acetate increased significantly in the MN-Gup group compared to the placebo group and before ingestion. Significant changes in the composition of gut microbiota were found after intake of MN-Gup yogurt when compared to placebo. The relative abundances of acetate-producing Bifidobacterium, Ruminoccaceae_UCG-002 and Ruminoccaceae_UCG-005 were significantly increased after intake of MN-Gup yogurt. These results showed that MN-Gup could relieve constipation related to increased acetate-producing Bifidobacterium, Ruminoccaceae_UCG-002 and Ruminoccaceae_UCG-005.

FECAL WET WEIGHT AND ELECTROLYTES IN ADULT PATIENTS WITH CHRONIC BENIGN INTESTINAL FAILURE / INSUFFICIENCY

Aim of this retrospective-observational study was to evaluate fecal wet weight (WW), sodium (Na), and potassium (K) 24 h-excretions in patients with intestinal failure (IF) and insufficiency (INS), according to the residual length of short bowel, in the nutrition and clinical practice. All in-patients with SBS – IICB, surgery > 3 months, admitted at the Unit of Clinical Nutrition were enrolled. They were divided into 3 groups according to clinical outcome as shown in table 1. Long term NPD treatment was administered in groups A and B. Pts in group C had an intestinal insufficiency that allowed them to preserve oral autonomy All patients had a free oral diet without significant difference between the groups. At each stage, fecal WW, sodium and potassium were evaluated on three-days collections and mean values were calculated. Ion concentration was determined according to Mayo Clinic Laboratory method performed on the Roche Cobas 6000 (Voskoboev 2015). Twenty five pts (M11/F14), age 54.6 ±28 yrs, were enrolled. Study results are shown in the table 2. Only in group B significant reductions of WW and Na were shown, contextually with intestinal rehabilitation. Data suggest that WW and sodium excretion could be decisive biomarkers in the nutritional approach of these patients. The spectrophotometric assay performed by Roche Cobas 6000, represents a simple and fast laboratory analysis which allows the clinician to have a routine tool in clinical management of patients.

Laxative and antioxidant effects of ramie (Boehmeria nivea L.) leaf extract in experimental constipated rats.

Ramie leaf (Boehmeria nivea L.) is rich in cellulose, polyphenol compounds, vitamin C, and minerals. The leaves of this plant, which are used for medicinal purposes, have long been reported to have anti‐inflammatory, antioxidant, anticolitis, and antidiabetic effects. We investigated the protective effects of ramie leaf ethanol extract (RLE) against loperamide‐induced constipation and oxidative stress in rats. Male Sprague‐Dawley rats were administered 200 or 400 mg/kg body weight of RLE (RLEL and RLEH groups) by gavage, while normal (NOR) and control (CON) rats received saline. Loperamide (4.0 mg/kg, twice per day) was injected subcutaneously to induce constipation in RLEL, RLEH, and CON groups. Total fecal number, wet weight, and water content decreased, while the total number of loperamide‐induced fecal pellets in the distal colon increased with administration of RLE in a dose‐dependent manner. Gastrointestinal transit time was more greatly reduced in RLE‐treated groups than in the CON group. Serum total cholesterol (TC) level, as well as alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activity, was significantly lower in both RLEL and RLEH groups compared with the CON group. Intestinal mucosa malondialdehyde (MDA) and hydrogen peroxide (H2O2) production decreased significantly in a dose‐dependent manner in the RLE‐treated groups. Loperamide decreased the antioxidant enzyme activity, including that of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), while RLE administration increased the antioxidant activity. These results suggest that RLE exerts potent laxative and antioxidant effects in model rats with loperamide‐induced constipation.

Effects of Extrinsic Wheat Fiber Supplementation on Fecal Weight; A Randomized Controlled Trial.

Higher fiber intake may confer beneficial effects on health. Our objective was to investigate the impact of 10 g extrinsic wheat fiber on fecal bulk. Therefore, we performed two randomized intervention studies in which we provided extrinsic wheat fiber-enriched products or appropriate control products for five days together with normal diet. In one trial, 10 participants received fiber-enriched food products, whereas in the second study, 19 participants supplemented their daily diet with fiber-enriched drinks. The main outcome variable of this intervention was fecal bulk. Other outcomes were gut microbiota composition, short chain fatty acids in feces, and stool consistency and frequency. Fecal wet weight was significantly increased (p < 0.02) with extrinsic wheat fiber-enriched foods. In contrast, ingestion of extrinsic wheat fiber in the form of drinks did not significantly change fecal wet weight. In both groups, fecal dry weight was not altered upon extrinsic wheat fiber supplementation. However, the intake of fiber-enriched foods resulted in higher acetic acid levels in feces compared to fiber-enriched drinks. Regarding gut microbiota profiles, extrinsic wheat fiber-enriched food products were not associated with substantial alterations. In conclusion, 10 g extrinsic wheat fiber added to a normal diet increased fecal bulk if administered in a solid food matrix, but not if applied in the form of drinks. DRKS, DRKS00015792.Registered 30 October 2018.

Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli

Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.

Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial

Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome. In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed. Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial. Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide. Zealand Pharma.

Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs.

Chronic constipation affects 14%-17% of the population. Elobixibat, a novel, ileal bile acid transporter (IBAT) inhibitor, has been approved as a new chronic constipation drug in Japan in January 2018. The present study aimed to examine the pharmacological effects of elobixibat on colonic motility in conscious dogs using a telemetry system. Six male beagle dogs were surgically implanted with strain gauge force transducers for gastrointestinal (GI) motility recording. The motility index was calculated from GI motility at each recording site in conscious and nonrestraint dogs. The fasted dogs were orally administered elobixibat (3, 10, or 30mg kg-1 ) or 30mg kg-1 of sennoside as positive control or vehicle using a crossover design and washout period of more than 6days. One hour after drug administration, the dogs were fed chow, and GI motility and defecation were observed for 10hours; GI motility was quantified to calculate giant migrating contractions (GMCs). Fecal bile acids (BAs) were determined as well. Elobixibat and sennoside significantly increased the number of defecations, fecal wet weight, and water content within 10hours after administration. Elobixibat dose-dependently decreased the time to first bowel movement, increased the amount of total fecal BAs, and rapidly induced mild GMCs during defecation; however, higher strength of GMCs was observed with sennoside. Elobixibat induces bowel movements faster than sennoside through a different mechanism. Elobixibat locally inhibits IBAT in the ileal lumen, leading to elevated fecal BAs in the colon and induced mild GMCs during defecation.

DSP-6952, a novel 5-HT4 receptor partial agonist, inhibits visceral hypersensitivity and ameliorates gastrointestinal dysfunction in experimental animals

The pharmacological profile of DSP-6952, a novel 5-HT4 receptor partial agonist, was investigated to evaluate the potential use for GI disorders, and to compare its effects in some GI dysfunction models with those of clinically efficacious prokinetic agents. DSP-6952 enhanced gastric motility and caused colonic giant migrating contractions (GMCs) associated with defecation in conscious dogs, having ED50 value for inducing GMCs of 1.56 mg/kg. DSP-6952 (3–10 mg/kg, i.g.) significantly enhanced colonic transit rate in guinea pigs; this enhancement was antagonized by SB-207266, a selective 5-HT4 receptor antagonist. DSP-6952 (1–10 mg/kg, p.o.) rapidly increased fecal wet weight without increasing fluid content in mice. Sennoside (30–100 mg/kg, p.o.) also increased fecal wet weight; however, it significantly increased fluid content with diarrhea. DSP-6952 dose-dependently improved clonidine- and morphine-induced delay in whole-gut transit in mice (ED50= 0.429 mg/kg and 0.310 mg/kg, respectively), which represented atonic and spastic constipation models, respectively. In viscerally hypersensitive rats treated with acetic acid, DSP-6952 (10 mg/kg, i.p., 30 mg/kg, p.o., 30 mg/kg, i.c.) and tegaserod (1 mg/kg, i.p.), but not prucalopride (10 mg/kg, i.p.), significantly inhibited the increase in colorectal distension-induced visceromotor response; these findings suggest that DSP-6952 and tegaserod inhibit visceral hypersensitivity in rats. It was concluded that DSP-6952, a novel and orally available 5-HT4 receptor agonist, induced colonic GMCs, enhanced colonic transit, increased defecation without inducing diarrhea, improved drug-induced delay in whole-gut transit, and inhibited visceral hypersensitivity in experimental animals. Therefore, DSP-6952 is expected to become a useful drug for treatment of IBS-C and chronic constipation.

Effects of Hemp seed soft capsule on colonic ion transport in rats.

AIMTo investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats.METHODSSprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d. The normal and constipation groups were treated with distilled water. After the treatment, the fecal wet weight and water content were measured. The basal short-circuit current (Isc) and resistance were measured by an Ussing Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug application experiment was also conducted. The accumulative concentrations of HSSC (0.1 mg/mL, 0.5 mg/mL, 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 10.0 mg/mL and 25.0 mg/mL) were added to the normal isolated colonic mucosa and the Isc was recorded. Further, after the application of either ion (Cl- or HCO3-) substitution, ion channel-related inhibitor (N-phenylanthranilic acid, glybenclamide, 4,4-diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway inhibitor [tetrodotoxin (TTX), atropine, or hexamethonium], the Isc induced by HSSC was also measured.RESULTSIn the constipation group, the fecal wet weight and the water content were decreased in comparison with the normal group (P < 0.01). After the treatment with HSSC, the fecal wet weight and the water content in the HSSC group were increased, compared with the constipation group (P < 0.01). In the constipation group, the basal Isc was decreased and resistance was increased, in comparison with the normal group (P < 0.01). After the treatment with HSSC, the basal Isc was increased (P < 0.05) and resistance was decreased (P < 0.01) in the HSSC group compared with the constipation group. In the in vitro experiment, beginning with the concentration of 1.0 mg/mL, differences in Isc were found between the experimental mucosa (with HSSC added) and control mucosa. The Isc of experimental mucosa was higher than that of control mucosa under the same concentration (1.0 mg/mL, P < 0.05; 2.5-25 mg/mL, P < 0.01). After the Cl- or HCO3- removal and pretreated with different inhibitors (cAMP-dependent and Ca2+-dependent Cl- channels, Na+-K+-2Cl- cotransporter (NKCC), Na+-HCO3- cotransporter or Cl-/HCO3- exchanger inhibitor), there were differences between experimental mucosa and control mucosa; the Isc of experimental mucosa was lower than that of control mucosa under the same concentration (P < 0.05). Meanwhile, after pretreatment with neural pathway inhibitor (TTX, atropine, or hexamethonium), there were no differences between experimental mucosa and control mucosa under the same concentration (P > 0.05).CONCLUSIONHSSC ameliorates constipation by increasing colonic secretion, which is mediated via the coaction of cAMP-dependent and Ca2+-dependent Cl- channels, NKCC, Na+-HCO3- cotransporter or Cl-/HCO3- exchanger.

Effect of Lactic Acid Bacteria-Fermented Mulberry Leaf Extract on the Improvement of Intestinal Function in Rats.

This study examined the laxative effects of mulberry leaf extract (MLE) fermented by lactic acid bacteria (LAB), which contains high levels of polyphenolic and flavonoid compounds, against loperamide-induced constipation in rats. Sprague-Dawley rats were divided into a normal group (N) and three experimental groups; loperamide treated group (C), loperamide and LAB-fermented MLE 300 mg/kg treated group (MLEL), and loperamide and LAB-fermented MLE 600 mg/kg treated group (MLEH). After 33 d, fecal pellet amount, fecal weight, water content of fecal, gastrointestinal transit time and length, and serum lipid profiles were measured. Constipation was induced via subcutaneous injection of loperamide (2.0 mg/kg b.w., twice a day) for the final 5 d of the experiment. After loperamide administration, the LAB-fermented MLE groups showed a significantly increase in the fecal pellets number, wet weight, and water content in rats compared with the C group. Moreover, increases in the intestinal length and viable Lactobacillus numbers in the feces were observed in the LAB-fermented MLE groups. The intestinal transit time was shorter in the LAB-fermented MLE groups than in the C group. In addition, the LAB-fermented MLE groups showed a significant decrease in triglyceride and total cholesterol levels and an increase in HDL-cholesterol level. These results indicated that oral administration of LAB-fermented MLE shows laxative effect in loperamide-induced constipated rats.

Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation

Chronic constipation is a highly common functional gastrointestinal disorder that adversely affects patient quality of life. At present, limited therapeutic options are available for the treatment of chronic constipation, which indicates the need for new therapeutic agents. Herein, we report the potential of mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1) inhibitor, for the amelioration of chronic constipation.Mizagliflozin's inhibitory activity against SGLTs was evaluated by an in vitro assay of cells transiently expressing SGLTs. The safety profile of an initial single dose (2–160mg, orally) and multiple doses (2–20mg, orally, once daily immediately prior to breakfast on Days 1 and 13, and three times daily immediately prior to every meal on Days 3–12) of mizagliflozin was determined by performing a phase I study in healthy male subjects. In addition, the effect of mizagliflozin and lubiprostone on fecal wet weight was compared using a dog model of loperamide-induced constipation and rat model of low-fiber-diet-induced constipation.Mizagliflozin potently inhibited human SGLT1 in a highly selective manner. The results of the phase I study showed mizagliflozin increased stool frequency and loosened stool consistency; these effects increased progressively with an increase in the dosage and the number of doses of mizagliflozin. In addition, the oral administration of mizagliflozin increased fecal wet weight in a dog model of loperamide-induced constipation and a rat model of low-fiber-diet-induced constipation, similar to lubiprostone.These results suggest the potential use of a novel selective SGLT1 inhibitor, mizagliflozin, for the amelioration of chronic constipation.

Electroacupuncture ameliorates abnormal defaecation and regulates corticotrophin-releasing factor in a rat model of stress.

ObjectiveTo examine the effect of electroacupuncture (EA) treatment on abnormal defaecation in a rat model of chronic heterotypic stress (CHS) and investigate the underlying mechanisms.Methods20 male Sprague-Dawley rats were randomly divided into three groups: normal (n=6), CHS (n=7), and CHS+EA (n=7). Rats in the CHS group and CHS+EA groups received four different types of stressors for 7 days. For rats in the CHS+EA group, EA was applied at ST36 in the bilateral hind legs for 30 min before each stress-loading session. Rats in the normal group did not receive stressors or EA treatment. The faecal pellets of each rat were collected and weighed at a fixed time every day. Protein expression of corticotrophin-releasing factor (CRF) in the hypothalamus and colorectal tissues was measured by Western blotting at the end of the experiment on the 7th day.ResultsAfter 7 consecutive days of CHS, the number of faecal pellets, faecal wet weight, and faecal water content were significantly increased in the CHS group compared with the normal group (p=0.035, p=0.008 and p=0.008, respectively). All three parameters were significantly decreased in CHS+EA versus CHS groups (p=0.030, p=0.011 and p=0.006, respectively). Stress significantly increased CRF expression in both the hypothalamus and colorectal tissues. The excessive CRF responses seen following CHS were significantly suppressed by EA treatment.ConclusionsEA treatment can ameliorate stress loading induced abnormal defaecation in rats and decrease protein expression of CRF centrally (hypothalamus) and peripherally (colorectal tissues), suggesting a potentially therapeutic role for EA in stress-related responses.

Resistant starch suppresses postprandial hypertriglyceridemia in rats

Postprandial increase in blood triglyceride levels is an independent risk factor for coronary artery disease, and dietary resistant starch (RS) is increasingly being considered for its contribution to disease prevention. Specifically, RS has beneficial effects on of the glycemic index, diabetes, cholesterol levels, and weight management. However, the effects of once-daily intake of RS on postprandial hypertriglyceridemia remain poorly characterized. In this study, the effects of a single administration of cornstarch-derived RS on postprandial increases in blood triglyceride levels were investigated in rats using oral fat tolerance/loading tests. Following the administration of lipid meals, increases in serum triglycerides levels were significantly reduced in rats fed corn oil containing 500mg/mL RS. Moreover, fecal lipid volumes and wet weights following lipid meals were significantly greater in rats fed corn oil containing 500mg/mL RS than in the corn oil only group, confirming the inhibition of dietary fat absorption. Finally, a significant positive correlation was observed between fecal lipid contents and wet weights in rats administered RS. These results suggest that RS intake with dietary fats induces defecation and confirm results of recent reports on the health-promoting potential of once-daily RS intake.