Mid-infrared spectroscopic identification of the right-baked rhubarb for ulcerative colitis therapy.

Clinical and experimental evidences have confirmed the significant therapeutic effects of rhubarb on ulcerative colitis (UC), but the strong purgative function of rhubarb also aggravates UC symptoms such as bloody diarrhea. Stir-baking to scorch is a traditional Chinese medicinal processing method that can eliminate the adverse purgative function while keep or even enhance the UC therapeutic function of rhubarb. However, the under-baked rhubarb still have the undesirable purgative function, but the over-baked rhubarb may lose the required medicinal functions. Therefore, the determination of the right endpoint is the primary quality concern about the baking process of rhubarb. In this research, typical anthraquinone compounds and mid-infrared (MIR) spectra were recruited to determine the best baking degree of rhubarb for UC therapy. Raw rhubarb slices were baked at 180 °C with rotation to prepare the rhubarbs with different baking degrees. The right-baked rhubarb was defined according to the UC therapeutic responses as well as the traditional color criterion. Referring to the typical anthraquinone compounds in rhubarb slices and extracts, the baking degree of rhubarb may be assessed by the conversion ratio of anthraquinone glycosides to anthraquinone aglycones. MIR spectra showed the gradual decompositions of organic compounds including anthraquinone glycosides and tannins during the baking process. Rhubarbs with different baking degrees can be distinguished clearly by MIR-based principal component analysis. In conclusion, the ratio of anthraquinone glycosides to anthraquinone aglycones may be a reasonable chemical indicator of the right-baked rhubarb. Meanwhile, MIR spectroscopy can identify the right-baked rhubarb simply and rapidly.

A novel purgative mechanism of multiflorin A involves changing intestinal glucose absorption and permeability.

BACKGROUND: Multiflorin A (MA) is a potential active ingredient of traditional herbal laxative, Pruni semen, with unusual purgative activity and an unclear mechanism, and inhibiting intestinal glucose absorption is a promising mechanism of novel laxatives. However, this mechanism still lacks support and a description of basic research. PURPOSE: This study aimed to determine the main contribution of MA to the purgative activity of Pruni semen and elucidate the effect intensity, characteristics, site, and mechanism of MA in mice, and determine the novel mechanism of traditional herbal laxatives from the perspective of intestinal glucose absorption. METHODS: We induced diarrhoea in mice by administering Pruni semen and MA, and the defecation behaviour, glucose tolerance, and intestinal metabolism were analysed. The effects of MA and its metabolite on peristalsis of the intestinal smooth muscle were evaluated using an intestinal motility assay in vitro. Intestinal tight junction proteins, aquaporins, and glucose transporters expression were analysed using immunofluorescence; gut microbiota and faecal metabolites were analysed using 16S rRNA and liquid chromatography-mass spectrometry. RESULTS: MA administration (20 mg/kg) induced watery diarrhoea in over half of the experimental mice. The activity of MA in lowering peak postprandial glucose levels was synchronous with purgative action, with the acetyl group being the active moiety. MA was metabolised primarily in the small intestine, where it decreased sodium-glucose cotransporter-1, occludin, and claudin1 expression, then inhibited glucose absorption, resulting in a hyperosmotic environment. MA also increased the aquaporin3 expression to promote water secretion. Unabsorbed glucose reshapes the gut microbiota and their metabolism in the large intestine and the increasing gas and organic acid promoted defecation. After recovery, the intestinal permeability and glucose absorption function returned, and the abundance of probiotics such as Bifidobacterium increased. CONCLUSION: The purgative mechanism of MA involves inhibiting glucose absorption, altering permeability and water channels to promote water secretion in the small intestine, and regulating gut microbiota metabolism in the large intestine. This study is the first systematic experimental study on the purgative effect of MA. Our findings provide new insight into the study of novel purgative mechanisms.

Effect of konjac glucomannan on metabolites in the stomach, small intestine and large intestine of constipated mice and prediction of the KEGG pathway.

The occurrence of constipation involves the whole gastrointestinal tract. Konjac glucomannan (KGM) has been clinically proven to alleviate constipation, but its mechanism has not been fully understood. The present study aimed to investigate the excretion-promoting effect of KGM on constipated mice and the underlying molecular mechanism. In this study, the UHPLC-QE orbitrap/MS method was used to determine the metabolic phenotypes of total gastrointestinal segments (i.e., the stomach {St}, small intestine {S}, and large intestine {L}) in constipated mice treated with KGM. The results showed that KGM improved the fecal water content, body weight growth rate, and serum gastrointestinal regulation related peptide levels. The metabolomics results revealed the decreased levels of amino acids, cholines, deoxycholic acid, arachidonic acid, thiamine and the increased levels of indoxyl sulfate, histamine, linoelaidic acid etc. The KEGG pathway analysis indicated that the relaxation effect of KGM supplementation was most likely driven by modulating the expression levels of various key factors involved in biosynthesis of amino acid (i.e., phenylalanine, tyrosine and tryptophan), linoleic acid metabolism, biosynthesis of secondary metabolites, and arachidonic acid metabolism signalling pathways. The results indicated that KGM alleviates constipation by regulating potential metabolite markers and metabolic pathways in different gastrointestinal segments.

Identification of rhein as the metabolite responsible for toxicity of rhubarb anthraquinones.

Rhubarb is a popular food in Europe with laxative properties attributed to anthraquinones. Long term usage of rhubarb anthraquinones has been linked to colonic toxicity, including the formation of melanosis coli, which is associated with increased risk of colon cancer. The major purgative anthraquinone in rhubarb is thought to be sennoside A, which is metabolised by colonic microflora. Here, we sought to identify the toxic metabolite responsible for melanosis coli in rats dosed with rhubarb anthraquinones for up to 90 days. Three metabolites were detected in rat faeces using HPLC. Of these, rhein was identified as the metabolite that accumulated most over time. Fecal flora from treated rats were capable of greater biotransformation of sennoside A to rhein compared to that from control rats. Cell culture experiments suggested that apoptosis and autophagy induced by rhein is the likely mechanism of chronic toxicity of rhubarb anthraquinones.

Purgative/laxative actions of Globularia alypum aqueous extract on gastrointestinal-physiological function and against loperamide-induced constipation coupled to oxidative stress and inflammation in rats.

BACKGROUND: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the effect of Globularia alypum L. leaves aqueous extract (GAAE) against loperamide (LOP)-produced constipation. METHODS: Animals were given LOP (3 mg/kg, b.w., i.p.) and GAAE (100, 200, and 400 mg/kg, b.w., p.o.) or yohimbine (2 mg/kg, b.w., i.p.), simultaneously, for 1 week. Gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods. KEY RESULTS: GAAE ameliorates significantly gastric emptying (64% to 76.5%) and intestinal transit (66.65% to 84.73%). LOP negatively influenced defecation parameters and generated a stress situation. GAAE administration in contrast ameliorated those parameters and re-established oxidative balance. CONCLUSION: GAAE showed a modest action against oxidative stress and decreased LOP effect and thereby can be considered a pharmacological agent in constipation.

Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson's Disease.

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson's disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.

Purging and the body in the therapeutic use of ayahuasca.

Ayahuasca is a psychoactive plant mixture used in ceremonial contexts throughout Western Amazonia. Its use has expanded globally in recent decades and become popular among westerners who travel to the Peruvian Amazon in increasing numbers to experience its reportedly healing effects. Through a review of relevant literature on Amazonian shamanism, combined with the authors' ethnographic data from shamanic tourism contexts of the Peruvian Amazon and neo-shamanic networks in Australia (collected between 2003 and 2015 - with a total of 227 people interviewed or surveyed, including healers and participants), we demonstrate that purging has been integral to the therapeutic use of ayahuasca across and beyond Amazonia. Therapeutic approaches to ayahuasca point to combined modulations of the gut and the mind, and the bodily and the social, that are expressed through discourse about healing and the body. Relating ethnographic evidence to recent scientific studies that connect the gut to emotional health, we do not approach the gut as merely biological ground on which cultural meanings are imposed, but rather as simultaneously physical and cultural. Based upon our analysis, we argue that ayahuasca purging should not be dismissed as a drug side effect or irrational belief but reconsidered for its potential therapeutic effects.

[Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation].

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.

Bowel Preparation for Colonoscopy in Children: 1 Day PEG-3350 with Bisacodyl versus 3 Day Sennosides.

BACKGROUND AND OBJECTIVES: Bowel preparation (BP) for colonoscopy is a challenging procedure in children and different regimens have been used for this purpose. Polyethylene glycol (PEG) is the most preferred agent in recent years. The primary aim of this study was to evaluate the efficacy of 1-day PEG-3350 with bisacodyl (PEG-B) and comparing it with 3-day sennosides A+B. METHOD: In this prospective, randomized, and single-blinded study, children aged 2-18 years were included in the PEG-B group for 1 day or in Senna group for 3 days. The effectiveness of BP was assessed according to the Ottawa and Boston BP scales, compliance and adverse effects were also recorded. Pre- and post-preparation biochemistry were obtained for investigation of safety of both regimens. RESULTS: Successful BP was observed in 88.3% (n = 53/60) of PEG-B and 86% (n = 55/64) of Senna groups according to Boston scale, and it was 85% (n = 51/60) and 84.4% (n = 54/64), respectively, according to Ottawa scale. The cecal intubation rate was 96.7% (n = 58/60) in the PEG-B group and 93.8% (n = 60/64) in the Senna group. Ease of administration and disturbance in regular daily activities was better in the PEG-B group (p < 0.05). There was no major adverse event and biochemical abnormality in both groups. The correlation between Ottawa and Boston scales was found to be excellent (r2 = -0.954, p < 0.01). CONCLUSIONS: The efficacy, safety, and adverse effect profile of 1-day BP with PEG-B regimen was found to be similar to 3-day sennosides regimen, however, the PEG-B regimen had advantages such as short duration, ease of administration, and better patient comfort. Also, high correlation rate between the Boston and Ottawa scales in pediatric patients was remarkable.

Investigation of the treatment of sand accumulations in the equine large colon with psyllium and magnesium sulphate.

Enteropathy associated with sand accumulation in the large colon of horses has been reported worldwide. Intestinal sand accumulations are commonly treated medically, but randomised controlled clinical trials on horses are scarce. This prospective study evaluated the efficacy of an enterally administered combination of psyllium and magnesium sulphate (MgSO4) for the removal of large colonic sand accumulations in horses without clinical signs of acute colic. The two groups comprised 20 untreated control horses and 20 horses treated with 1g/kg bodyweight (bwt) of psyllium and 1g/kg bwt of MgSO4 administered by nasogastric intubation once daily for 4 days. Both groups had no access to soil during the study period. The amounts of accumulated sand were evaluated radiographically before and after treatment. Significantly more treated horses cleared their sand accumulations than horses in the control group. This clearance was determined by observing the estimated quantity by area of sand remaining in the large colon (P<0.001) and by comparing the numbers of successfully treated horses (P=0.004) between the two groups after 4days of treatment. However, there were unexplained individual variations in the clearance of sand accumulation.

Bowel preparation in CT colonography: Is diet restriction necessary? A randomised trial (DIETSAN).

OBJECTIVES: To investigate whether diet restriction affects quality of colon cleansing and patient tolerance during reduced bowel preparation for CT colonography (CTC). METHODS: Asymptomatic and symptomatic patients were enrolled in this pragmatic, single-centre, randomised trial. All patients were randomly assigned (1:1 ratio, blocks of ten) to receive a reduced bowel preparation and faecal tagging with (Diet-Restriction-Group [DR]) or without (No-Diet-Restriction-Group [NDR]) dietary restriction. Five readers performed a blinded subjective image analysis, by means of 4-point Likert-scales from 0 (highest score) to 3 (worst score). Endpoints were the quality of large bowel cleansing and tolerance to the assigned bowel preparation regimen. The trial is registered at ClinicalTrial.gov (URomLSDBAL1). RESULTS: Ninety-five patients were randomly allocated to treatments (48 in NDR-group, 47 in DR-group). Both groups resulted in optimal colon cleansing. The mean residual stool (0.22, 95%CI 0.00-0.44) and fluid burden (0.39, 95%CI 0.25-0.53) scores for patients in DR-group were similar to those in patients in NDR-group (0.25, 95%CI 0.03-0.47 [p = 0.82] and 0.49, 95%CI 0.30-0.67 [p = 0.38], respectively). Tolerance was significantly better in NDR-group. CONCLUSION: A reduced bowel preparation in association with faecal tagging and without any dietary restriction demonstrated optimal colon cleansing effectiveness for CTC, providing better patient compliance compared with dietary restriction. KEY POINTS: • Dietary restriction in reduced bowel preparation regimen can be avoided. • The quality of colon cleansing is not affected by dietary restriction. • The quality of faecal tagging is not affected by dietary restriction. • Avoidance of dietary restriction improves patients' tolerance for CTC.

Resin glycosides from Convolvulaceae plants.

Resin glycosides are well known as purgative ingredients, which are characteristic of certain crude drugs such as Mexican Scammony Radix, Orizabae Tuber, and Jalapae Tuber, all of which originate from Convolvulaceae plants. Depending on their solubility in ether, these are roughly classified into two groups-jalapin (soluble) and convolvulin (insoluble). Almost all jalapins hitherto isolated and characterized had common intramolecular macrocyclic ester structures. These are composed of 1 mol of oligoglycoside of hydroxyl fatty acid (glycosidic acid) partially acylated by some organic acids at the sugar moiety, some examples of which are ester-type dimers. On the other hand, convolvulin is regarded as an oligomer of a variety of acylated glycosidic acids. This review describes the isolation and structural elucidation of resin glycosides from some Convolvulaceae plants, including Ipomoea operculata, Pharbitis nil, Quamoclit pennata, Calystegia soldanella, and I. muricata.

Preparation of Clinically Useful Sennoside-reduced Rhubarb.

OBJECTIVE: The aim of this study was to develop a method of removing sennoside to reduce the cathartic effect of rhubarb while conserving its other pharmacological activities. METHODS: Rhubarb powder was steam autoclaved at 121°C and 0.14 MPa for 20, 60, or 120 minutes, and HPLC analysis was conducted to determine levels of rhubarb components. Mice were fed non-autoclaved or 20-minute-autoclaved rhubarb extracts. Feces were collected and weighed over a 24-hour period. India ink was orally administered to determine the distance of fecal migration through the intestinal tract. RESULTS: Autoclaving 20, 60, and 120 minutes decreased sennoside A and B to trace levels but only autoclaving 20 minutes conserved most of the (+)-catechin, (-)-epicatechin, and (-)-epicatechin gallate contents (i.e., 69%, 90%, 88%, respectively). Therefore only rhubarb autoclaved for 20 minutes was used in subsequent experiments. Fecal output (in g) in mice treated with water (control), autoclaved rhubarb, and non-autoclaved rhubarb was 2.78 ± 0.07, 3.30 ± 0.13 (p = 0.348), and 3.81 ± 0.07 (p = 0.005). India ink migration was far less in mice treated with autoclaved rhubarb vs non-autoclaved rhubarb. CONCLUSION: Steam autoclaving the rhubarb for 20 minutes reduces sennoside levels and its cathartic activity while conserving its other pharmacological activities.

Estimated GFR Decline Following Sodium Phosphate Enemas Versus Polyethylene Glycol for Screening Colonoscopy: A Retrospective Cohort Study.

BACKGROUND: Associations between sodium phosphate enemas and nephropathy have raised concerns about the safety of use as part of a bowel-cleansing regimen administered prior to colonoscopies. The objectives of this analysis are to evaluate the impact of sodium phosphate enema versus polyethylene glycol powder for oral solution (PEG) use prior to colonoscopy screening on estimated glomerular filtration rate (eGFR) decline in Veterans Affairs (VA) patients and identify other risk factors contributing to eGFR decline. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 70,499 VA patients receiving sodium phosphate enemas (with or without PEG) or PEG alone prior to colonoscopy screenings. PREDICTOR: Use of either sodium phosphate or PEG. OUTCOMES: A 50% increase in serum creatinine level over a 15-month, over a 6-week, and between a 9- and 15-month period was used to define any, acute, or long-term eGFR decline, respectively. MEASUREMENTS: Multivariable logistic regressions estimated the likelihood of eGFR decline conditional on the use of sodium phosphate enemas versus PEG alone, controlling for potential confounders. RESULTS: A greater proportion of patients using sodium phosphate enemas versus PEG had any (P<0.001) or long-term (P=0.003) eGFR declines, whereas similar proportions had acute eGFR declines (P=0.9). In the adjusted analyses, use of sodium phosphate enemas (± PEG was associated with an increased likelihood of having any (OR, 1.3; 95% CI, 1.2-1.5) or long-term (OR, 1.4; 95% CI, 1.1-1.8) eGFR decline, but not acute eGFR decline (OR, 1.0; 95% CI, 0.6-1.7). Other risk factors for eGFR decline included diabetes and non-iron deficient anemia. LIMITATIONS: Unobserved heterogeneity due to volume depletion and potential selection bias due to higher-risk patients preferentially prescribed sodium phosphate enemas. CONCLUSIONS: Use of sodium phosphate enemas versus PEG alone prior to colonoscopy screening increases the risk for VA patients having long-term eGFR decline. Patients with non-iron deficient anemia are at particularly high risk for eGFR decline. These findings motivate the need to re-examine prescribing practices for sodium phosphate enemas as part of a bowel-cleansing regimen.

Sulphated Polysaccharide Isolated from the Seaweed Gracilaria caudata Exerts an Antidiarrhoeal Effect in Rodents.

Diarrhoea is a significant health problem for children in developing countries that causes more than 1 million deaths annually. This study aimed to evaluate the antidiarrhoeal effect of sulphated polysaccharide (PLS) from the alga Gracilaria caudata in rodents. For the evaluation, acute diarrhoea was induced in Wistar rats (150-200 g) by administration of castor oil (10 mg/kg). Then, different parameters, including enteropooling and gastrointestinal transit and its pharmacological modulation by opioid and cholinergic pathways, were assessed using activated charcoal in Swiss Mice (25-30 g). Secretory diarrhoea was examined using cholera toxin (CT) (1 mg/loop)-treated, isolated intestinal loops from Swiss mice (25-30 g), which were also used to examine fluid secretion, loss of chloride ions into the intestinal lumen and absorption. In addition, a GM1-dependent ELISA was used to evaluate the interaction between PLS, CT and the GM1 receptor. Pre-treatment with PLS (10, 30 and 90 mg/kg) reduced faecal mass, diarrhoeal faeces and enteropooling. However, 90 mg/kg more effectively reduced these symptoms; therefore, it was used as the standard dose in subsequent experiments. Gastrointestinal transit was also reduced by PLS treatment via a cholinergic mechanism. Regarding the diarrhoea caused by CT, PLS reduced all study parameters, and the ELISA showed that PLS can interact with both the GM1 receptor and CT. These results show that PLS from G. caudata effectively improved the parameters observed in acute and secretory diarrhoea, which affects millions of people, and may lead to the development of a new alternative therapy for this disease.

Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons.

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

[Advance in studies on effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma, as a commonly used traditional Chinese medicine, has been widely applied in clinic. Its major purgative constituent is anthraquinones, which are believed to be a toxic ingredient. Glycyrrhizae Radix et Rhizoma has been reputed as the best alexipharmic to moderate medicine natures. In this paper, the effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma was studied in two aspects--the boiling process and intestinal metabolism; Studies on combined administration of Glycyrrhizae Radix et Rhizoma and Rhei Radix et Rhizoma in recent years were summarized according to chemical constituent, intestinal flora, I/II phase metabolism and drug transport. However, the material basis and mechanism for their compatibility remain unclear, further studies will be made in the future.

Breath methane in functional constipation: response to treatment with Ispaghula husk.

BACKGROUND: Colonic fermentation produces hydrogen (H2 ), and also produces methane (CH4 ) in subjects with methanogenic flora (M+). Methane production has been associated with chronic constipation (CC) and with changes in gut motility. To determine CH4 production in CC compared to controls, and to assess whether the therapeutic response to Ispaghula husk in CC differs between CH4 -producers and non-producers. METHODS: Forty-eight patients with functional constipation or irritable bowel syndrome-constipation and 19 healthy age-and-sex-matched volunteers (HV) filled in a 1-week symptom diary and a dietary questionnaire. They then underwent a lactulose breath test (LBT) to measure H2 and CH4 production (peak and area under the time-concentration curve, AUC-) and a colonic transit time (CTT) assessment. In patients, measurements were repeated after a 4-week treatment with Ispaghula husk. KEY RESULTS: Prevalence of M+ in patients was 60.5% vs 52.6% in HV (p = 0.37). Patients had significantly longer CTT and greater production of both H2 and CH4 during LBT. There was a significant correlation between CH4 production and CTT (r = 0.51; p = 0.07). Treatment response rate was similar for M+ and M- patients (58.3% vs 52.9%; p = 0.76) as were the increases in bowel movements and Bristol score, changes in abdominal discomfort and bloating. In M+, treatment reduced CTT (-10 ± 35 h; p = 0.029 vs baseline) and CH4 levels: peak CH4 (-13 ± 24 ppm; p = 0.014) and CH4 -AUC (-817 ± 3100 ppm/min; p = 0.04). CONCLUSIONS & INFERENCES: Although CH4 production has been associated with CC pathophysiology, we found that CH4 status did not negatively affect the response to Ispaghula husk treatment. The measurement of CH4 levels as a biomarker tool for CC requires further appraisal.

Comparison of the effects of enteral psyllium, magnesium sulphate and their combination for removal of sand from the large colon of horses.

Prospective studies documenting the efficacy and side effects of medical treatment for colonic sand accumulation in horses are limited. The purpose of the study was to compare the effect of enteral administration of magnesium sulphate (MgSO4), psyllium mucilloid (psyllium), and a combination of MgSO4 and psyllium on the evacuation of large accumulations of sand in the large colon of adult horses. Thirty-four horses with naturally acquired, large sand accumulations (>5 cm × 15 cm) identified on abdominal radiography were randomly allocated to one of three treatment groups: (1) 1 g/kg psyllium (n = 12); (2) 1 g/kg MgSO4 (n = 10), or (3) their combination (n = 12). Treatments were administered once a day via nasogastric intubation and continued for a total of 4 days. Lateral radiographs of the ventral abdomen were repeated on day 4 of treatment. If the area of sand in the radiographic image was <25 cm(2) on day 4, the sand accumulation was considered resolved. Of 12 horses treated with a combination of psyllium and MgSO4, nine evacuated the sand from the ventral colon within 4 days. In comparison, only 3/12 horses treated with psyllium and 2/10 horses treated with MgSO4 resolved (both significantly different from the combination; P <0.05). Large accumulations of sand in the large colon of horses can be treated medically. Administering a combination of psyllium and MgSO4 via nasogastric intubation once daily for a total of 4 days was a more effective treatment than either constituent alone.

Purgative components in rhubarbs: adrenergic receptor inhibitors linked with glucose carriers.

Rhubarbs and their extractives have been used as cathartic for many years. There have been numerous breakthroughs in the pharmacological research of the drug. However, as the key point of the mechanism, the targets of the effective components still remain unclear. In this paper, with an in vitro system of isolated intestine, we found that both the rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore, computer based docking provided the binding model of the anthraquinone derivatives and adrenergic receptor. Then, based on the results of the small intestinal promotion and purgative effect experiments in vivo, we built an "inhibitor-carrier" hypothesis to elucidate the mechanism of rhubarb. This work provided key massages for the pharmacological research of rhubarb, such a common and active medicinal plant, and might be of help for the development of new purgative drugs.