Pharmacological Basis for the Antidiarrheal and Antispasmodic Effects of Cuminaldehyde in Experimental Animals: In Silico, Ex Vivo and In Vivo Studies.

BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum.

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum / 中国结合医学杂志

OBJECTIVE@#To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro.@*METHODS@#In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA).@*RESULTS@#GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil.@*CONCLUSIONS@#GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicology of Species from the Genus Ajuga L.: A Systematic Review.

The present review is aimed at providing a comprehensive summary of the botanical characteristics, ethnomedicinal uses, phytochemical, pharmacological, and toxicological studies of the genus Ajuga L. The extensive literature survey revealed Ajuga L. species to be a group of important medicinal plants used for the ethnomedical treatment of rheumatism, fever, gout, sclerosis, analgesia, inflammation, hypertension, hyperglycemia, joint pain, palsy, amenorrhea, etc., although only a few reports address the clinical use and toxicity of these plants. Currently, more than 280 chemical constituents have been isolated and characterized from these plants. Among these constituents, neo-clerodane diterpenes and diterpenoids, phytoecdysteroids, flavonoids, and iridoids are the major bioactive compounds, possessing wide-reaching biological activities both in vivo and in vitro, including anti-inflammatory, antinociceptive, antitumor, anti-oxidant, antidiabetic, antimicrobial, antifeedant, antidiarrhoeal, hypolipidemic, diuretic, hypoglycaemic, immunomodulatory, vasorelaxant, larvicidal, antimutagenic, and neuroprotective activity. This review is aimed at summarizing the current knowledge of the ethnomedicinal uses, phytochemistry, biological activities, and toxicities of the genus Ajuga L. to reveal its therapeutic potentials, offering opportunities for future researches. Therefore, more focus should be paid to gathering information about their toxicology data, quality-control measures, and the clinical application of the bioactive ingredients from Ajuga L. species.

Ethnobotanical, phytochemical and therapeutic effects of Myrtus communis L. berries seeds on gastrointestinal tract diseases: a review.

Medicinal plants have always had an important place in the therapeutic arsenal of humanity and particularly in the treatment of gastrointestinal tract diseases. Myrtus communis L., known as common myrtle, is native to Southern Europe, North Africa, and Western Asia. The different parts of this plant are used as antiinflammatory, antiulcer, antidiabetic, urinary antiseptic, and to treat the respiratory and digestive systems diseases. For the first time, an exhaustive bibliographic research of the seeds of myrtle berries has been carried out. As a result, it has been found that this plant is very rich in biologically active compounds such as phospholipids, polyunsaturated fatty acids, and phenolic compounds. This has made it effective in the treatment of digestive diseases. In order to emphasize the importance of myrtle berries seeds, this review has been established by discussing its botanical, morphological, phytochemical, ethnomedicinal studies as well as its effect on digestive tract diseases.

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.

Efficacy and safety of Entoban for the treatment of chronic diarrhea.

The current randomized clinical trial was conducted to assess the safety and effectiveness of Entoban for treating patients of chronic diarrhea. The study enrolled 150 patients fulfilling the inclusion criteria, among them 95 were males and 55 were females. Written informed consent was obtained from all study participants. Metronidazole tablets (400 mg) were used in a control group for 7-10 days. The test group received Entoban capsule 400mg every 8 hours for five days. Primary outcome of the study was daily bowel frequency evaluation; the secondary outcome was evaluation of clinical symptoms including abdominal pain, distention, stool consistency and sensation of incomplete evacuation. The study is registered at (https://register.clinicaltrials.gov) having registration number NCT02642250. In an intention-to-treat (ITT) analysis, it has been observed that 39(84.78%) in test group and 37(78.72%) in control group showed complete improvement. Participants in the test group exhibited a marked reduction in symptoms; the symptom score was decreased from 3 (maximum) to 1 (minimum) or 0 (absent) in most of participants. Major difference was observed regarding side effects reported between two treatment groups (p value <0.0001). Entoban possesses considerable therapeutic efficacy for the treatment of chronic diarrhea analogous with the conventional Metronidazole therapy.

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.

Protective effect of Dalbergia sissoo Roxb. ex DC. (family: Fabaceae) leaves against experimentally induced diarrhoea and peristalsis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia sissoo Roxb. ex DC. (family: Fabaceae; Indian Rosewood), is used in India, especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to substantiate the claim of therapeutic success of the plant species in diarrhoea. AIM: To study the protective effect of ethanol extract from D. sissoo Roxb. ex DC. leaves (EDSL) against experimentally induced diarrhoea and peristalsis in mice. MATERIALS AND METHODS: Castor oil-induced diarrhoea and magnesium sulphate (MgSO4)-induced diarrhoea tests were used to assess the antidiarrhoeal activity of D. sissoo. Gastrointestinal tract transit of charcoal meal test and barium sulphate milk was used to assess the peristalsis activity of the extract, while the acute toxicity study and determination of total phenolics and total flavonoids were carried out using well-established protocols and methods. RESULTS: The EDSL significantly reduced faecal output in castor oil-induced and MgSO4-induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. D. sissoo significantly delayed the onset of diarrhoea induced by both castor oil and MgSO4 and comparable to loperamide, a standard antidiarrhoeal drug. Both D. sissoo and atropine sulphate significantly reduced the peristalsis activity of charcoal meal and barium sulphate milk in mice. The preliminary phytochemical analysis of EDSL revealed the presence of carbohydrates, phenolics, glycosides, and flavonoids. The median lethal dose of EDSL was greater than 2000 mg/kg (orally (p.o.)). CONCLUSION: The data obtained indicate that the EDSL has antidiarrhoeal and antiperistalsis activities and thus supports its traditional use. The data also show that the plant material given p.o. may be safe and/or non-toxic in mice.

Effect of the interaction of seaweed extracts containing laminarin and fucoidan with zinc oxide on the growth performance, digestibility and faecal characteristics of growing piglets.

Seaweed extracts (SWE) rich in laminarin and fucoidan have shown promise as a supplement for weaned piglets. However, successful application in pig nutrition depends on their bioactivity in the presence of additives such as ZnO. In the present study, a 2 × 2 factorial experiment was carried out to investigate the effect of the interaction between SWE and ZnO on the growth performance, digestibility and faecal characteristics of 192 weaned piglets (6·5 kg). The piglets were penned in groups of 4 (n 12 pens). The study consisted of two phases after weaning: a starter diet period from the day of weaning (0 d) to 21 d and a transition diet period from 21 to 40 d. The dietary treatments were as follows: (1) control diet; (2) control diet+ZnO; (3) control diet+SWE; (4) control diet+ZnO+SWE. Diets containing ZnO improved the faecal consistency of the piglets throughout the experimental period (0-40 d). An effect of the interaction between ZnO and SWE on several variable was observed. The diet containing only SWE or ZnO improved the feed conversion efficiency of the piglets during the transition diet period; however, this effect was not observed when the diet containing both ZnO and SWE was fed. The diet containing only SWE increased the N and organic matter digestibility of the piglets; however, this effect was not observed in the presence of ZnO. An interaction between ZnO and SWE was observed, whereby the faecal counts of Escherichia coli were decreased when piglets were fed the diet containing only SWE, but not when fed the diet containing both SWE and ZnO. In summary, SWE and ZnO improve growth performance when given alone, but not when given in combination. The biological effect of SWE on selected digestibility and faecal characteristics was markedly different when compared with that of ZnO.

Calcium ameliorates diarrhea in immunocompromised children.

Treatment of infectious diarrheas remains a challenge, particularly in immunocompromised patients in whom infections usually persist and resultant diarrhea is often severe and protracted. Children with infectious diarrhea who become dehydrated are normally treated with oral or intravenous rehydration therapy. Although rehydration therapy can replace the loss of fluid, it does not ameliorate diarrhea. Thus, during the last decades, there has been continuous effort to search for ways to safely stop diarrhea. Herein, we report 3 immunocompromised children who developed severe and/or protracted infectious diarrhea. Their diarrheas were successfully "halted" within 1 to 2 days following the administration of calcium.

Antinociceptive, antidiarrheal, and neuropharmacological activities of Barringtonia acutangula.

CONTEXT: Barringtonia acutangula (L.) Gaertn. (Lecythidaceae) has been used in folk medicine in the treatment of arthralgia, chest pain, dysmenorrhea, inflammation, hemorrhoids, diarrhea, and also in psychological disorders. OBJECTIVE: To investigate the antinociceptive, antidiarrheal, and neuropharmacological effect of the methanol extract of B. acutangula leaves and seeds in mice. MATERIALS AND METHODS: The extracts (200 and 400 mg/kg; p.o.) were tested for antinociceptive activity by acetic acid-induced writhing, hot plate and tail immersion models; castor oil- and magnesium sulphate-induced diarrheal models were used to evaluate antidiarrheal activity whereas hole cross and open field models were employed for testing neuropharmacological activity. RESULTS: Both extracts exhibited significant antinociceptive effect (p < 0.001) in acetic acid and heat induced pain models in a dose-dependent manner. The extracts prolonged the latency period to the thermal stimuli in both hot plate and tail immersion test. The extracts also showed significant inhibition of defecation (p < 0.001, 0.01) in both diarrheal models. Again, the spontaneous motor activity was decreased (p < 0.001) by the extracts in both hole cross and open field test. DISCUSSION AND CONCLUSION: The results of this study suggest that the methanol extracts of B. acutangula leaves and seeds possess good antinociceptive, antidiarrheal, and central nervous system (CNS) depressant activities. This study validates the use of this plant in traditional medicine.

Antidiarrhoeal activity of DAS-77 (a herbal preparation).

BACKGROUND: DAS-77 is a traditional herbal preparation composed of the young callous bark of mango (Mangifera indica Linn., Anacardiaceae) and the dried root of pawpaw (Carica papaya Linn., Caricaceae). This phytomedicine is claimed to have beneficial effects in the treatment of gastrointestinal disorders, including diarrhoea. OBJECTIVE: To investigate the antidiarrhoeal effect of DAS-77 using standard pharmacological models. METHODS: Normal and castor oil-induced intestinal transit, and castor oil-induced diarrhoea tests wore carried out in mice while intestinal fluid accumulation and gastric emptying tests were carried out in rats. Acute toxicity test and preliminary phytochemical analysis were also conducted. RESULTS: The results obtained in this study revealed that DAS-77 had no significant inhibitory effect on normal intestinal transit, castor oil-induced diarrhoea, intestinal fluid accumulation and gastric emptying. However, the inhibitory effect of DAS-77 was significant (p<0.001) relative to control in the castor oil-induced intestinal transit test. Peak effect was produced at the dose of 100 mg/kg (p.o.). The effect of DAS-77 in this respect was reversed by pilocarpine and propranolol, but not by phenoxybenzamine. DAS-77 did not produce any mortality given p.o. up to 10 g/kg, indicating the relative safety of the preparation. The i.p. LD50 was estimated to be 1122 mg/kg. The remedy was found to contain saponins, tannins, phenols and alkaloids. CONCLUSION: Findings in this study suggest that DAS-77 possesses antidiarrhoeal activity due to the inhibition of intestinal motility possibly mediated by muscarinic and alpha adrenergic receptors.

Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis rotundifolia Triana (Melastomataceae).

BACKGROUND: The leaves of Dissotis rotundifolia are used ethnomedically across Africa without scientific basis or safety concerns. Determination of its phytochemical constituents, antimicrobial activity, effects on the gastrointestinal tract (GIT) as well as toxicological profile will provide supportive scientific evidence in favour of its continous usage. METHOD: Chemical and chromatographic tests were employed in phytochemical investigations. Inhibitory activity against clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhi were compared with Gentamycin. Our report includes minimum inhibitory concentration (MIC) against the tested organisms. The effect of the ethanol extract on the motility of the GIT in mice using the charcoal plug method and castor oil induced diarrhoea in rats was evaluated. Toxicological evaluation was determined by administering 250 mg/kg and 500 mg/kg of extracts on male Wistar rats for 14 days with normal saline as control. The tissues of the kidneys, liver, heart and testes were examined. RESULTS: Phytochemical studies revealed the presence of alkaloids, saponin and cardiac glycosides. The crude ethanol extract and fractions inhibited the growth of E. coli, P. aeruginosa, S. aureus and S. typhi to varying extents. The degree of transition exhibited by the charcoal meal was dose-dependent. In the castor oil induced diarrhoea test, all the doses showed anti-spasmodic effects. The LD50 in mice was above 500 mg/kg body weight. Toxicological evaluation at 500 mg/kg showed increased cytoplasmic eosinophilia and densely stained nuclei of the liver, tubular necrosis of the kidney, presence of ill-defined testes with indistinct cell outlines and no remarkable changes in the heart. CONCLUSION: Ethanol extracts of Dissotis rotundifolia have demonstrated antimicrobial activity against clinical strains of selected microorganisms. The plant showed potential for application in the treatment of diarrhoea, thereby justifying its usage across Africa. It also demonstrated toxicity in certain organs at the dose of 500 mg/kg, and it will be necessary to fully establish its safety profile.

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.

Therapy of inflammatory bowel diseases in pregnancy and lactation.

Inflammatory bowel diseases (IBDs) are a group of disorders characterised by chronic or relapsing inflammation within the gastrointestinal tract of variable severity. A chronic medication is often needed and management of fertile women is a crucial point because of the possible adverse effects associated with the administered drugs and the disease itself. The risk of pregnancy-related complications and the disease behaviour during pregnancy depends mainly on disease activity at time of conception. So, it is very important to plan the pregnancy and reach and maintain a clinical remission of the disease before conception. Drugs usually used in IBD treatment include 5- aminosalicylic acid compounds, corticosteroids, azathioprine and 6-mercaptopurine, cyclosporine A, mesalazine, and antibiotics such as metronidazole and ciprofloxacin. Management of IBD in pregnancy at present is not standardised or supported by strong evidence. In this report, we summarise the available data, mainly derived from retrospective and case-control studies, about IBD management in pregnancy, focusing mostly on the safety of drugs during gestation and peripartum.

Antidiarrhoeal and intestinal modulatory activities of Wei-Chang-An-Wan extract.

AIM OF THE STUDY: Wei-Chang-An-Wan (WCAW), a traditional pharmaceutical preparation, has been used for treating various gastrointestinal (GI) diseases for several decades, but it is still poorly understood how it works on those disorders. This study was to investigate the effects of WCAW extract on GI tract. MATERIALS AND METHODS: The activities of the methanol extract (ME) of WCAW on castor oil-induced diarrhoea, gastrointestinal transit (GIT) in mice, and contractions of isolated rabbit jejunum were investigated. We further assessed the safety of ME in vivo. Additionally, a HPLC fingerprint of ME was appraised to ensure its chemical consistency. RESULTS: Ten peaks were identified in the HPLC fingerprint of ME. At the doses of 400 and 800 mg/kg, ME significantly protected mice against castor oil-induced diarrhoea as well as the number of faeces and wet faeces. Interestingly, administration of ME significantly accelerated GIT in normal mice and reduced stimulated GIT induced by neostigmine. ME also dose-dependently attenuated spontaneous contractions of the isolated rabbit jejunum, and those induced by acetylcholine (Ach) and neostigmine. Moreover, oral administration of ME up to 5 g/kg did not produce any toxic effects. Taken together, ME is able to inhibit diarrhoea, increase normal GIT, and decrease GIT induced by neostigmine, which indicate that ME might play a bidirectional role in GI tract. CONCLUSIONS: Our study provides a scientific basis for the clinical use of WCAW.

Clinical role of diosmectite in the management of diarrhea.

BACKGROUND: Diosmectite (DS), an antidiarrheal absorbent natural clay, was proposed for treatment of acute gastroenteritis and more recently considered for diarrhea within the functional bowel disorder syndrome. OBJECTIVE: To review pharmacology efficacy, mechanisms of action and safety of DS. METHODS: We consulted PubMed/Medline using the keywords of smectite and diarrhea or gastroenteritis, and reviewed most recent recommendations by scientific societies. CONCLUSIONS: Solid data show that DS is effective in infectious diarrhea, mainly as an ion antisecretory agent and in preventing intestinal damage. Despite clinical data being consistent and convincing, DS is not considered as first-line treatment because of the presence of alternative therapeutic options. However, it definitely may play a role in infectious colitis, where treatment options are less convincing. Some available evidences demonstrate a role of DS in functional diarrhea.

Safety evaluation of Elixir Paregorico in healthy volunteers: a phase I study.

A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whether Elixir Paregorico administration causes any noticeable toxic effects in healthy volunteers. In all, 28 middle-aged healthy male (n = 14) and female (n = 14) were enrolled. After screening and a washout period, eligible subjects received four oral doses per day of Elixir Paregorico (3 mL diluted in 30 mL of water) over a 10-day period. Altogether, all 28 participants completed the study. The results of hematological and biochemical tests performed pre and post-treatment were within the normal range. In both male and female volunteers, there were no statistical differences (P > 0.05) in the results of clinical and laboratory tests performed at screening, on 5th and 10th day visits, and at final assessment. Although mild adverse events were related, which subsided spontaneously, no serious untoward reactions were reported following Elixir Paregorico administration. To our knowledge, this is the first demonstration that Elixir Paregorico administered four times a day for 10 days is safe and does not cause any noticeable toxic effect in healthy volunteers.

Investigation of Alternanthera repens and Bidens odorata on gastrointestinal disease.

Alternanthera repens and Bidens odorata are used as medication for gastrointestinal diseases today, mainly in relation to diarrhea; therefore, pharmacological tests with aqueous and ethanol extracts of both species were carried out in mice. Using charcoal meal, the activity of the four extracts on intestinal motility was determined, finding that they inhibit the advance of the gastrointestinal content. Also, the lethal media doses were estimated in order to examine the plants' safety. The data confirmed the validity of the medicinal use for both plant species, contributing to explain the use of these plants as antidiarrheal agents in Mexican traditional medicine.