Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies.

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.

Hetong decoction relieves loperamide-induced constipation in rats by regulating expression of aquaporins.

OBJECTIVE: To investigate whether Hetong decoction (, HTT) alleviates constipation via regulating AQPs expression. METHODS: Constipation in rats was induced by loperamide, and rats were randomly assigned into model (saline), HHT-low (95 g/kg), HTT-medium (190 g/kg), HTT-high (380 g/kg) and positive control (mosapride) groups. Then the defecation function, the concentration of serum arginine vasopressin (AVP) and cyclic adenosine monophosphate (cAMP), and the expression of AQP3 and AQP8 in colon tissues were assessed. NCM460 colon cells with AQP3 and AQP8 knockdown or overexpression were exposed to serum from rats that received low or high dose of HTT, followed by detection of AQP3 and AQP8 expression. RESULTS: The model group showed lower fecal weight and water content, weaker intestinal transit, higher serum concentration of AVP and cAMP, increased proximal and distal AQP8 expression, increased proximal but decreased distal AQP3 expression. However, these trends were reversed in both the HTT group (low, medium and high dose) and the positive control group. In NCM460 cells, HTT dose-dependently stabilized AQP3 and AQP8 expression under AQP3/8 plasmid interference or overexpression. CONCLUSIONS: HTT relieves constipation in rats through regulating AQP3 and AQP8 expression.

Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats.

Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.

Extraction of Pectin from Orange Peel and Study of Its Protective Effect Against Loperamide-Induced Impaired Gastrointestinal Motor Functions and Oxidative Stress in Rats.

Pectin is a polysaccharide attached to carbohydrates. These are substances exclusively of plant origin. The aim of the present study is to evaluate the laxative effects of orange peel pectin extract (OPPE) against constipation induced by loperamide (LOP) in rats. Rats were equally divided into six groups and treated daily 1 week as follows: Control, LOP (3 mg/kg, body weight [b.w.], Per Os [p.o.]), LOP+yohimbine (2 mg/kg, b.w., i.p.), and LOP+OPPE (6.25, 12.5, and 25 mg/kg, b.w., p.o.). At the end of the experiment, the effects of OPPE were assessed by fecal parameters (numbers, weight, and water content), gastrointestinal transit, gastric emptying, serum metabolic parameter changes, intestinal and colon mucosa oxidative stress, and the histological examination. The defecation test showed that administration of LOP (3 mg/kg, b.w., p.o.) leads to the production of remarkable constipation. Indeed, the number and water content of stools decreased (25.50 [n/24 h] and 29.86%) significantly (P < .05). Acute pretreatment with OPPE significantly and dose dependently accelerated the stool moistening and allowed an increase of stool weight (2.85, 3.61, 3.93 [g/24 h/rat]) as well as the frequency of defecation (47.36, 54.54, and 56.26 [n/24 h]). OPPE also significantly (P < .05) and dose dependently increased the intestinal motility (70.78%, 73.33%, and 75.01%) and gastric emptying. LOP-induced reduction (P < .05) of intestinal secretion was accompanied by a colonic and small bowel oxidative stress status and histological changes, which was attenuated by OPPE treatment. The findings of this study indicate that OPPE possesses an important role in the gastrointestinal motility regulation, and thus lend pharmacological credence to the suggested use of the natural pectin for the treatment, management, and/or control of constipation.

Electro-hydrodynamic assisted synthesis of lecithin-stabilized peppermint oil-loaded alginate microbeads for intestinal drug delivery.

Peppermint oil (PO) is the most prominent oil using in pharmaceutical formulations with its significant therapeutic value. In this sense, this oil is attracting considerable attention from the scientific community due to its traditional therapeutic claim, biological and pharmacological potential in recent research. An organic solvent-free and environment-friendly electrohydrodynamic assisted (EHDA) technique was employed to prepared PO-loaded alginate microbeads. The current study deals with the development, optimization, in vitro characterization, in vivo gastrointestinal tract drug distribution and ex-vivo mucoadhesive properties, antioxidant, and anti-inflammatory effects of PO-loaded alginate microbeads. The optimization results indicated the voltage and flow rate have a significant influence on microbeads size and sphericity factor and encapsulation efficiency. All these optimized microbeads showed a better drug release profile in simulated intestinal fluid (pH 6.8) at 2 h. However, a minor release was found in acidic media (pH 1.2) at 2 h. The optimized formulation showed excellent mucoadhesive properties in ex-vivo and good swelling characterization in intestine media. The microbeads were found to be well distributed in various parts of the intestine in in vivo study. PO-loaded alginate microbeads similarly showed potential antioxidant effects with drug release. The formulation exhibited possible improvement of irritable bowel syndrome (IBS) in MO-induced rats. It significantly suppressed proinflammatory cytokines, i.e., interleukin- IL-1ß, and upregulated anti-inflammatory cytokine expression, i.e., IL-10. It would be a promising approach for targeted drug release after oral administration and could be considered an anti-inflammatory therapeutic strategy for treating IBS.

Comparative study of the laxative effects of konjac oligosaccharides and konjac glucomannan on loperamide-induced constipation in rats.

Dietary fiber is the basic therapeutic method to relieve the symptoms of chronic constipation. The aim of this study was to compare the laxative effect of konjac glucomannan (KGM) and konjac oligosaccharides (KOS) on constipated rats. KGM and KOS were administered to loperamide-induced constipated rats at dosages of 100 mg per kg bw and 400 mg per kg bw for 15 days. Feces were collected to evaluate the defecation function. X-ray imaging and an electrophysiological system were used to determine gastrointestinal (GI) motility. Immunohistochemistry and western blotting were used to measure the protein levels. Magnetic resonance imaging (MRI) was performed to assess flatulence. Our results demonstrated that low-dose KOS (L-KOS) exerted the best laxative effect. Compared to the normal control (NC) group, the fecal number in the L-KOS group increased by 39.4%, and the fecal weight significantly increased by 31.9% which was higher than those in the low-dose KGM (L-KGM) and high-dose KGM (H-KGM) groups. The fecal moisture content and transit scores were significantly increased only in the L-KOS group. Meanwhile, less GI gas was produced by KOS. Additionally, further investigations suggested that KOS could upregulate the protein expression of stem cell factors (SCF)/c-kit, and significantly promoted the secretion of mucus. In conclusion, compared to KGM, KOS had a conspicuous laxative effect especially at a low dosage. The potential laxative mechanisms of KOS probably are regulating the SCF/c-kit signalling pathway and increasing mucus secretion. These findings indicated that as a kind of functional oligosaccharide, KOS is more conducive to alleviating constipation compared to polysaccharides.

The protective effects of yellow tea extract against loperamide-induced constipation in mice.

Yellow tea, a rare type tea from China, has a rich breadth of functional ingredients and benefits the gastrointestinal tract. However, it is not clear whether the yellow tea extract can alleviate constipation. Therefore, we used loperamide-induced constipation in mice to evaluate the effects of yellow tea extract. Fifty Kunming mice were randomly divided into five groups: normal, model, low-dose yellow tea extract, low-dose yellow tea extract prevention group, and high-dose yellow tea extract prevention group. Mice were administered yellow tea extract for 5 weeks followed by loperamide-induced constipation for the final 2 weeks. The results showed that yellow tea extract alleviated constipation symptoms by improving the fecal water content, defecation weight, and gastrointestinal transit rate. Yellow tea extract intervention also protected colon tissue, regulated serum neurotransmitters, and decreased the vasoactive intestinal peptide level. Furthermore, qRT-PCR indicated that yellow tea extract regulated genes associated with the constipation state, raised 5-HT3 and 5-HT4 and reduced AQP3 and AQP4 mRNA expression. Moreover, we found that yellow tea extract changed the gut microbiota composition. Community diversity and richness were increased and principal co-ordinate analysis demonstrated that the yellow tea extract prophylaxis groups differed from the model group. Difference analysis indicated that yellow tea extract increased Roseburia, Lachnospiraceae_UCG-006, and Bifidobacterium and decreased norank_f_Clostridiales_vadinBB60_group, unclassified_o_Bacteroidales, and Bacteroides, which are correlated with constipation. Based on these results, we believe that regular yellow tea consumption can effectively alleviate constipation.

Pediococcus pentosaceus B49 from human colostrum ameliorates constipation in mice.

Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.

Laxative Activity of the Hot-Water Extract Mixture of Hovenia dulcis Thunb. and Phyllostachys pubescens Mazel in Chronic Constipation Model SD Rats.

This study examined the laxative effects of hot-water extracts of Hovenia dulcis Thunb. (HD), Phyllostachys pubescens Mazel (PM), and a 2:8 mixture of both (HP) in two chronic constipation models. For the loperamide-induced constipation model, animals were divided into an untreated group, negative control group (loperamide 4 mg/kg), positive control group (bisacodyl 4 mg/kg) group, and six treatment groups (HP 100 or 400, HD 50 or 100, and PM 100 or 400 mg/kg). For the lowfiber diet-induced constipation model, animals were divided into an untreated group (normal diet), negative control group (low-fiber diet), positive control group (Agio granule, 620 mg/kg), and the same treatment groups. Fecal number, weight, fecal water content, and intestinal transit ratio were higher in the groups treated with HP, HD, and PM than in the groups treated with loperamide or lowfiber diet. Thickness of colon mucosa and muscle layers were increased in the treated groups. Colon tension increased in the HP groups, and [Ca2+]i measurements using fura-2 as an indicator showed that HP inhibits ATP-mediated Ca2+ influx in IEC-18 cells. These results showed that the HP mixture has laxative activity by increased mucin secretion and inducing contractile activity and relaxation. It may be a useful therapeutic strategy for ameliorating in chronic constipation.

Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice.

This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.

Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation.

Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. Meanwhile, more than 50% of patients are dissatisfied with sense of use of non-prescriptional laxatives. ß-glucans are natural polysaccharides widely found in yeast, fungus, and plants, which have been reported to exhibit various pharmacological effects. The aim of this study was to characterize the effect of ß-glucans extracted from the bread yeast cell wall on loperamide-induced constipation mice. Forty mice were fed with loperamide (10 mg/kg) to make the constipation model and a diet supplemented with 2.5, 5, and 10 mg/kg ß-glucan. We assessed the defecation frequency, intestinal transit function of mice, as well as used high-throughput sequencing to analyze the intestinal microbiota composition and functional biological profiles data. Meanwhile, we detected expression of neurotransmitters including acetylcholinesterase, substance P, and serotonin (5-HT) and expression of tight junction protein (TJP) including zonula occludens-1 and mucin-2 in distal colon to characterize the possible molecular mechanisms. ß-glucans significantly enhanced intestinal motility and provided a possibility to regulate the expression of neurotransmitters and TJP in mice. The intestinal microecological portion of the treatment group partially recovered and was closer to the normal group. This study showed that ß-glucans can influence the intestinal microbiota and restore microecological balance to regulate the express of neurotransmitters and TJP to recover intestinal epithelial mechanical barrier. We suggested that ß-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis.

Laxative effects of triple fermented barley extracts (FBe) on loperamide (LP)-induced constipation in rats.

BACKGROUND: Constipation, a common health problem, causes discomfort and affects the quality of life. This study intended to evaluate the potential laxative effect of triple fermented barley (Hordeum vulgare L.) extract (FBe), produced by saccharification, Saccharomyces cerevisiae, and Weissella cibaria, on loperamide (LP)-induced constipation in Sprague-Dawley (SD) rats, a well-established animal model of spastic constipation. METHODS: Spastic constipation was induced via oral treatment with LP (3 mg/kg) for 6 days 1 h before the administration of each test compound. Similarly, FBe (100, 200 and 300 mg/kg) was orally administered to rats once a day for 6 days. The changes in number, weight, and water content of fecal, motility ratio, colonic mucosa histology, and fecal mucous contents were recorded. The laxative properties of FBe were compared with those of a cathartic stimulant, sodium picosulfate. A total of 48 (8 rats in 6 groups) healthy male rats were selected and following 10 days of acclimatization. Fecal pellets were collected one day before administration of the first dose and starting from immediately after the fourth administration for a duration of 24 h. Charcoal transfer was conducted after the sixth and final administration of the test compounds. RESULTS: In the present study, oral administration of 100-300 mg/kg of FBe exhibited promising laxative properties including intestinal charcoal transit ratio, thicknesses and mucous producing goblet cells of colonic mucosa with decreases of fecal pellet numbers and mean diameters remained in the lumen of colon, mediated by increases in gastrointestinal motility. CONCLUSION: Therefore, FBe might act as a promising laxative agent and functional food ingredient to cure spastic constipation, with less toxicity observed at a dose of 100 mg/kg.

Synergic Laxative Effects of an Herbal Mixture of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia in Loperamide-Induced Constipation of Sprague Dawley Rats.

Constipation is an acute or chronic illness attributed to various causes, ranging from lifestyle habits to side effects of a disease. To improve the laxative effects of some traditional medicines, herbal mixtures of Liriope platyphylla, Glycyrrhiza uralensis, and Cinnamomum cassia (LGC) were evaluated for their mechanism of action and therapeutic effects in loperamide (Lop)-induced constipated Sprague Dawley rats by examining alterations in excretion parameters, histological structure, mucin secretion, and related protein levels. Food intake and water consumption were constant for all animals. We observed that the Lop+LGC-treated group had significantly greater excretion of stool and urine than was observed in the Lop+Vehicle-treated group. Administration of LGC in the constipation model restored the intestinal transit ratio to normal levels, and increased the number of goblet cells, mucosal layer, and muscle thickness. Mucin secretion was greater in the Lop+LGC-treated group than in the Lop+Vehicle-treated group, and the expression of MUC2 and AQP8 genes were also increased. In addition, reverse transcription polymerase chain reaction and Western blot revealed an increase in the muscarinic acetylcholine receptors (mAChRs) in the Lop+LGC-treated group compared to the Lop+Vehicle-treated group. Furthermore, compared with the Lop+Vehicle-treated group, treatment with LGC reduced the phosphorylation of PKC and PI3K, and expression of Gα protein, but increased levels of IP3. Our results suggest that the traditional herbal mixture of LGC induces a potent laxative effect in Lop-induced constipation through mucosal tissue changes and mucin production. We also demonstrated that the laxative effect of LGC is closely related to the expression of mAChR and its downstream signals, suggesting the possibility of developing a constipation-laxative agent using LGC.

Gallotannin-Enriched Extract Isolated from Galla Rhois May Be a Functional Candidate with Laxative Effects for Treatment of Loperamide-Induced Constipation of SD Rats.

Several natural products containing tannins are used as traditional medicines for treatment of constipation; however, their pharmacological mechanism is not well understood. The laxative effects of gallotannin-enriched extract isolated from Galla Rhois (GEGR) were investigated using a constipation model induced by loperamide (Lop) injection. After analysis for antioxidant activity of GEGR, alterations in the excretion parameters, histological structure, mucin secretion, and related protein levels were measured in the transverse colon of Sprague Dawley (SD) rats with Lop-induced constipation following treatment with 250, 500 and 1,000 mg/ml of GEGR. The number and weight of feces increased significantly by 48-79% and 128-159%, respectively, in the Lop+GEGR treated group relative to the Lop+vehicle treated group, while food intake and water consumption were maintained at a constant level. The thickness of mucosa, muscle and flat luminal surface, as well as the number of goblet cells and crypt of lieberkuhn were enhanced in the Lop+GEGR treated group. Moreover, mucin secretion increased significantly in a dose dependent manner in the Lop+GEGR treated group. Furthermore, the downstream signaling pathway of the muscarinic acetylcholine receptors (mAChR) M2 and M3 was recovered by GEGR treatment, although the expression level varied. The levels of Gα expression and inositol triphosphate (IP3) concentration were also recovered in the Lop+GEGR treated group relative to the Lop+vehicle treated group. The results of the present study provide strong evidence that tannins distributed in various medicinal plants are important candidates for improving chronic constipation induced by Lop treatment in animal models.

Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial.

BACKGROUND: Fecal incontinence is a devastating condition with few US Food and Drug Administration-approved pharmacologic treatment options. Loperamide and psyllium, both first-line treatments, have different mechanisms of action without any comparative data. OBJECTIVE: The purpose of this study was to examine the effectiveness and tolerability of loperamide compared with psyllium for reducing fecal incontinence. We hypothesized that psyllium fiber supplementation would be more effective than loperamide for reducing fecal incontinence episodes and have fewer adverse effects. DESIGN: We conducted a randomized, double-blind, placebo-controlled crossover trial comparing loperamide (followed by psyllium) with psyllium (followed by loperamide). SETTINGS: Our sites included outpatient clinics within a Veterans Affairs medical center and university affiliate. PATIENTS: Participants included community-dwelling adults (n = 80) with at least 1 fecal incontinent episode on a 7-day bowel diary. INTERVENTION: Participants received either daily loperamide (plus placebo psyllium powder) or psyllium powder (plus loperamide placebo) for 4 weeks. After a 2-week washout, participants crossed over to 4 weeks of alternate treatment. MAIN OUTCOME MEASURES: The primary outcome was the number of fecal incontinence episodes from 7-day bowel diaries. Secondary outcomes included symptom severity, quality of life, and tolerability. RESULTS: Mean age was 60.7 ± 10.1 years; 68% were men. After determining nonsignificant carryover effects, combined analyses showed no differences between the loperamide and psyllium groups for reducing fecal incontinent episodes, symptom severity, or quality of life. Within each group, both loperamide and psyllium reduced fecal incontinent episodes and improved symptom severity and quality of life. Constipation occurred in 29% of participants for loperamide vs 10% for psyllium. LIMITATIONS: Limitations include the washout period length and dropout rate after crossing over to the second intervention. CONCLUSIONS: Both loperamide and psyllium improve fecal incontinence. Loperamide was associated with more adverse effects, especially constipation.

The effect of Aloe ferox Mill. in the treatment of loperamide-induced constipation in Wistar rats.

BACKGROUND: Constipation is the most common gastrointestinal complaint all over the world and it is a risk factor of colorectal cancer. In this study, the efficacy of aqueous leaf extract of Aloe ferox Mill. was studied against loperamide-induced constipation in Wistar rats. METHODS: Constipation was induced by oral administration of loperamide (3 mg/kg body weight) while the control rats received normal saline. The constipated rats were treated with 50, 100 and 200 mg/kg body weight/day of the extract for 7 days during which the feeding characteristics, body weight, fecal properties and gastrointestinal transit ratio were monitored. RESULTS: The extract improved intestinal motility, increased fecal volume and normalized body weight in the constipated rats, which are indications of laxative property of the herb with the 200 mg/kg body weight of the extract showing the best efficacy. CONCLUSION: The effect of the extract compares favourably well with senokot, a standard laxative drug. These findings have therefore, lent scientific credence to the folkloric use of the herb as a laxative agent by the people of the Eastern Cape of South Africa.

Anti-diarrhoeal activity of crude aqueous extract of Rubia tinctorum L. roots in rodents.

The anti-diarrhoeal effect of aqueous extract of Rubia tinctorum L. (Rubiaceae) roots in rodents was examined. At doses 300, 600 and 800 mg/kg aqueous extract protected rats, in a dose-dependent fashion, against castor oil-induced diarrhoeal dropping by 37, 59 and 64% respectively. Furthermore, it has significantly inhibited by 41% the gastrointestinal transit of charcoal in mice at 800 mg/kg dose of extract. These data suggest that Rubia tinctorum showed antidiarrhoeal activity by inhibiting intestinal motility which was concordant with its use in traditional medicine.

Irritable bowel syndrome: a mild disorder; purely symptomatic treatment.

(1) Patients frequently complain of occasional bowel movement disorders, associated with abdominal pain or discomfort, but they are rarely due to an underlying organ involvement. Even when patients have recurrent symptoms, serious disorders are no more frequent in these patients than in the general population, unless other manifestations, anaemia, or an inflammatory syndrome is also present; (2) There is currently no way of radically modifying the natural course of recurrent irritable bowel syndrome; (3) The effects of antispasmodics on abdominal pain have been tested in about 20 randomised controlled trials. Pinaverium and peppermint essential oil have the best-documented efficacy and only moderate adverse effects. Antispasmodics with marked atropinic effects do not have a favourable risk-benefit balance; (4) Tricylic antidepressants seem to have only modest analgesic effects in this setting. In contrast, their adverse effects are frequent and they have somewhat negative risk-benefit balances. Nor has the efficacy of selective serotonin reuptake inhibitor antidepressants (SSRIs) been demonstrated; (5) Alosetron and tegaserod carry a risk of potentially life-threatening adverse effects and therefore have negative risk-benefit balances; (6) Seeds of plants such as psyllium and ispaghul, as well as raw apples and pears, have a limited impact on constipation and pain. Osmotic laxatives are effective on constipation. Symptomatic treatments for constipation can sometimes aggravate abdominal discomfort; (7) Loperamide has been poorly assessed in patients with recurrent irritable bowel syndrome with diarrhoea. It modestly slows bowel movement but does not relieve pain or abdominal discomfort; (8) Dietary measures have not been tested in comparative trials. Some patients are convinced that certain foods provoke a recurrence of irritable bowel syndrome, but restrictive diets carry a risk of nutritional deficiencies; (9) Various techniques intended to control emotional and psychological disturbances have been proposed, including relaxation, biofeedback, hypnosis, and psychotherapy. The results of clinical trials are not convincing; (10) Oral products containing live bacteria, designed to change the equilibrium of intestinal flora, have been tested in 13 placebo-controlled trials, with inconsistent results. A few cases of septicaemia have been reported; (11) The six available trials of acupuncture (versus sham acupuncture) showed no more than a placebo effect; (12) In practice, patients who have recurrent irritable bowel syndrome but with no other signs of a condition warranting specific treatment should be reassured as to the harmless nature of their disorder if a careful physical examination and basic laboratory tests are negative. The only available treatments have purely symptomatic effects and only limited efficacy. It is best to avoid using all treatments and additional diagnostic investigations that carry a risk of disproportionate adverse effects.

Effects of fasting on evaluation of gastrointestinal transit with charcoal meal.

INTRODUCTION: At the present time, most studies investigating gastrointestinal transit time with charcoal are conducted in fasted rats. It seems reasonable to hypothesize that the fasting state of rats could influence the effect a compound had on gastrointestinal transit time. The purpose of this study was to investigate the effects of food on the pharmacological effects on gastrointestinal transit. METHODS: For each drug investigated, two sets of 32 male Sprague-Dawley rats were used. One set was studied after being fasted for approximately 6 h, the second set was studied after free access to food. Each set had 4 groups of animals (n=8/group) that were administered different doses, allowing the assessment of the drug effect after fasting and after free access to food. Animals were administered 0, 10, 25, and 75 mg/kg of morphine; 0, 10, 20, and 40 mg/kg loperamide, or 0, 0.05, 0.5, and 3.0 mg/kg clonidine. At predetermined times, an activated charcoal suspension was administered by oral gavage. Thirty minutes after receiving the charcoal meal, rats were euthanized and the small intestine was removed. The length of the small intestine and the distance traveled by the charcoal were recorded. For each animal, gastrointestinal transit was calculated as the percentage of the distance traveled relative to the total length of the small intestine. RESULTS: Baseline (vehicle dosed animals) gastrointestinal transit was significantly greater in fasted versus fed rats. In fasted rats, morphine did not have a significant effect on transit. In fed rats, 25 and 75 mg/kg morphine caused a significant decrease in transit. In fed and fasted rats, 0.5 and 3 mg/kg clonidine caused a significant decrease in transit. Loperamide did not affect gastrointestinal transit in fed or fasted rats at doses up to 40 mg/kg. DISCUSSION: These data demonstrate that food does not reduce the sensitivity of the gastrointestinal transit time.