Study on Anti-Constipation Effects of Hemerocallis citrina Baroni through a Novel Strategy of Network Pharmacology Screening.

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.

In vivo acute toxicity, laxative and antiulcer effect of the extract of Dryopteris Ramose.

Dryopteris ramosa (D. ramosa) is one of the most traded medicinally important plants of Himalayan region. Apart from other uses, D. ramosa is traditionally also used to treat gastric ulcers and as a laxative. The present study was designed to investigate the role of methanolic crude extract of Dryopteris Ramosa (MEDR) in acute toxicity, against loperamide induced constipated mice model, antiulcer effect of methanolic extract of D. Ramosa and cholinomimetic like effect of methanolic extract of D. Ramosa. The crude extract was investigated for the presence of active compounds (secondary metabolites) such as alkaloids, flavonoids, carbohydrates, glycosides, terpenoids, phenolic compounds, saponins, and tannins following the standard methods. The antiulcer effect was investigated in mice using the ethanol induced ulcer model at various doses i.e. 50 mg/kg, 100 mg/kg and 200 mg/kg doses. Constipation was induced in the mice via loperamide (3mg/kg body weight). The control group received normal saline. Different doses of plant extracts (50, 100, 150 and 200 mg/kg body weight/day) were administered for 7 days. Various parameters like feeding characteristics, gastrointestinal transit ratio, body weight, fecal properties and the possible mechanism of action of D. Ramosa on intestinal motility were monitored. Various Phytochemicals like saponins, glycosides, flavonoids, tannins, phenols, carbohydrate, alkaloids and triterpenes were found in D. Ramosa. The acute toxicity study showed that MEDR was associated with no mortality except mild and moderate sedation at the highest tested doses (1500 and 2000 mg/kg). MEDR also showed significant antiulcer activity against ethanol-induced ulcerogenesis. The extract enhanced the intestinal motility, normalized the body weight of constipated mice and increased the fecal volume which are indications of laxative property of the herb. The 200 mg/kg body weight dose of the extract was found effective. The presence of various Phytochemicals such as flavonoids, glycosides and tannins might be responsible for the antiulcer activity of D. Ramosa. This study provides the scientific background for the folkloric use of D. Ramosa as antiulcer agent. The laxative action of the extract compares positively with Duphalac, (standard laxative drug). These findings have therefore evidence scientific background to the folkloric use of the herb as a laxative agent.

Laxative Effects of Phlorotannins Derived from Ecklonia cava on Loperamide-Induced Constipation in SD Rats.

This study investigated the laxative effects of phlorotannins (Pt) derived from Ecklonia cava (E. cave) on chronic constipation by evaluating alterations in stool parameters, gastrointestinal motility, histopathological structure, mucin secretion, gastrointestinal hormones, muscarinic cholinergic regulation, and fecal microbiota in SD rats with loperamide (Lop)-induced constipation subjected to Pt treatment. Stool-related parameters (including stool number, weight, and water contents), gastrointestinal motility, and length of intestine were significantly enhanced in the Lop+Pt-treated group as compared to the Lop+Vehicle-treated group. A similar recovery was detected in the histopathological and cytological structure of the mid-colon of Lop+Pt-treated rats, although the level of mucin secretion remained constant. Moreover, rats with Lop-induced constipation subjected to Pt treatment showed significant improvements in water channel expression, gastrointestinal hormone secretions, and expression of muscarinic acetylcholine receptors M2/M3 (mAChRs M2/M3) and their mediators of muscarinic cholinergic regulation. Furthermore, the Lop+Pt-treated group showed a significant recovery of Bifidobacteriaceae, Muribaculaceae, Clostridiaceae, and Eubacteriaceae families in fecal microbiota. Taken together, these results provide the first evidence that exposure of SD rats with Lop-induced constipation to Pt improves the constipation phenotype through the regulation of membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.

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.

Studies on antidiarrheal and laxative activities of aqueous-ethanol extract of Asphodelus tenuifolius and underlying mechanisms.

BACKGROUND: Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant. METHODS: Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques. RESULTS: Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300-700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K+ (80 mM) and K+ (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca+ 2 concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists. CONCLUSION: The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca+ 2 channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca+ 2 influx through voltage gated Ca+ 2 channels. The study supports ethnic uses of the plant in diarrhea and constipation.

The Manufacturing Process of Kiwifruit Fruit Powder with High Dietary Fiber and Its Laxative Effect.

Kiwifruit is rich in vitamins, minerals, dietary fiber and other functional components, and it has long been used as a functional food to treat intestinal ailments such as constipation. The current research made full use of the kiwifruit, the juice was prepared by microencapsulation, and the dietary fiber in kiwifruit pomace was modified by enzymatic hydrolysis and grinding, then, the two were mixed to obtain an ultra-micro kiwifruit powder (UKP). In addition, the laxative effect of the UKP was verified by a diphenoxylate induced constipated mice model. The results demonstrated that compared with the raw samples, the retention rate of vitamin C, lutein and catechin in UKP were 83.3%, 81.9% and 88.3%, respectively, thus effectively avoiding the loss of functional components during the processing of kiwifruit. Moreover, α-amylase, protease and the ball milling process effectively reduced the size of dietary fiber in kiwifruit pomace, and its water-holding capacity (WHC), oil-holding capacity (OHC) and swelling capacity (SWC) were enhanced by 1.26, 1.65 and 1.10 times, respectively. Furthermore, to analyze the laxative effect of the UKP, a constipation mice model was established by diphenoxylate treatment (5 mg·kg-1, i.g.) for the last week, with or without UKP supplementation (2.4 g·kg-1 B.W. per day) for 4 weeks. The results demonstrated that UKP significantly increased feces condition (fecal output and dejecta moisture content, gut transit (the intestinal propulsion rates) and substance P (SP) levels in portal vein plasma, and it decreased the whole gut transit time and mucinogen granules secreted by goblet cell in constipated mice.

Combination of a hot-melt subcoating and an enteric coating for moisture protection of hygroscopic Sennae fructus tablets.

The objective of this study was to investigate the efficiency of moisture protection of hot-melt coatings solely and in combination with an enteric coating on hygroscopic tablet cores containing a spray-dried Sennae fructus extract. Tablet cores were subcoated with different hot-melt coating materials: medium chain tryglycerides, stearic acid, Precirol® ATO 5, and Compritol® 888 ATO, at varying amounts and coated with Eudragit® L 30D-55 for enteric resistance. Subcoating penetration, tablet disintegration, dissolution times, tablet hygroscopicity, and tablet properties such as weight, height, diameter, and hardness were analyzed. 3 mg/cm2 of tablet surface seemed to be sufficient if sustained release is not required. Thereby, hot-melt coating did not adversely affect the tablet properties with regard to subsequent processing steps. Compared to the tablet cores it was possible to reduce the moisture uptake by 85% at 75% relative humidity with tablets coated with a combination of Precirol® ATO 5 and Eudragit® L 30D-55. This combination was more efficient than high amounts of Eudragit® L 30D-55. Hot-melt coating proved to be a suitable technique for the application of subcoating material to tablet cores serving as a barrier against water permeation into hygroscopic tablet cores without exceeding the required disintegration times.

Evaluation of prokinetic and laxative effects of Hippophae rhamnoides in rodents.

Hippophae rhamnoides (Family; Elaeagnaceae) fruit extract was investigated for prokinetic and gut excitatory effects to rationalize its therapeutic utility in gastrointestinal complaints like delayed gastric emptying and constipation. The fruit extract of Hippophae rhamnoides (Hr.Cr) prepared in hydro-methanol (30:70) was verified for flavonoids, tannins, coumarins and terpenes as plant constituents. In mice, Hr.Cr administration caused an increased in faecal production and charcoal meal transport (50-300mg/kg, per-oral.), similar to activity pattern of carbamylcholine (1 mg/kg). Laxative and prokinetic effects of Hr.Cr were found partially atropine-sensitive. On challenge with isolated intestinal tissues, Hr.Cr charged a dose-dependent spasmogenic effect on jejunum (0.01-1mg/mL) preparations of rabbit and in ileal tissues (guinea-pig) at the dose range of 0.03 to 3mg/mL, following predominant relaxing impact at increased concentrations. Unlike carbamylcholine, stimulant effect of Hr.Cr was partly antagonized in atropine incubated tissues. These data attest the laxative, prokinetic and gut excitatory activities of Hippophae rhamnoides probably mediated through partial activation of muscarinic receptors. Further in agreement of the current findings with earlier reports on gastric emptying effects of Hippophae rhamnoides seed oil, this is the first study of its kind providing insight into mechanism to the laxative potential of Hippophae rhamnoides fruit, thus rationalizing its medicinal use in constipation.

PEG 3350 Administration Is Not Associated with Sustained Elevation of Glycol Levels.

OBJECTIVE: To determine whether trace amounts of ethylene glycol (EG), diethylene glycol (DEG), or triethylene glycol (TEG) in PEG 3350 are associated with increased blood levels of EG, DEG, or TEG in children receiving daily PEG 3350 therapy. STUDY DESIGN: Blood samples were drawn from 9 children who were being treated for constipation with PEG 3350 (6-12 years old) before and every 30 minutes for 3 hours after receiving 17 g of PEG 3350. PEG 3350, tap water, and blood samples from 18 age- and sex-matched controls also were analyzed. RESULTS: Baseline blood levels of EG and TEG did not differ between control and treated groups. DEG levels (median [IQR]) were lower in the PEG 3350 group (40.13 ng/mL [36.69, 63.94] vs 92.83 ng/mL [51.06, 128.93], P = .008). After PEG 3350 dose, levels of EG (390.51 ng/mL [326.06, 624.55]) and TEG (2.21 ng/mL [0, 4.5]) peaked at 90 minutes at 1032.81 ng/mL (826.84, 1486.13) (P = .009) and 35.17 ng/mL (15.81, 45.13) (P = .0005), respectively. DEG levels did not significantly change. Standard 17-g doses of PEG 3350 in 8 oz (237 mL) of water resulted in concentrations (mean ± SD) of EG, DEG, and TEG of 1.32 ± 0.23 µg/mL, 0.18 ± 0.03 µg/mL, and 0.12 ± 0.01 µg/mL, respectively. EG, DEG, and TEG levels in public water supply were 0.07 µg/mL, 0.21 µg/mL, and 0.02 µg/mL, respectively. CONCLUSIONS: Daily PEG 3350 therapy in children was not associated with sustained elevation of EG, DEG, or TEG blood levels over levels in matched controls. Although EG and TEG levels increased after a standard dose of PEG 3350, their peak values remained well below toxic levels.

Laxative Effects of Total Diterpenoids Extracted from the Roots of Euphorbia pekinensis Are Attributable to Alterations of Aquaporins in the Colon.

This study was designed to evaluate the toxic effects of total diterpenoids extracted from the roots of Euphorbia pekinensis (TDEP) on the mouse colon and to clarify the mechanism. Dried powdered roots of E. pekinensis were extracted with chloroform, and then the extract (6.7 g) was subjected to column chromatography and preparative TLC, giving TDEP. Using the HPLC-DAD method, the purity of TDEP was determined as 85.26%. Mice were orally administered with TDEP (3.942, 19.71 and 39.42 mg/kg), after which fecal water content and colon water content were examined. Both of them increased over time after TDEP administration, accompanied by severe diarrhea. Three hours after TDEP administration, the animals were sacrificed to obtain their colons. The mRNA and protein expression levels of aquaporin 1 (AQP1), AQP3 and AQP4 in the colon were measured using real-time RT-PCR and Western blotting, respectively. TDEP significantly increased the levels of AQP3 and AQP4, but decreased that of AQP1 in dose-dependent manners. Similarly, Pekinenin C, a casbane diterpenoid, significantly increased AQP3 protein and mRNA expressions in human intestinal epithelial cells (HT-29). Histopathological examination revealed that the colon was not significantly damaged. The laxative effects of E. pekinensis were associated with the alterations of AQPs in the colon by TDEP.

Effect of Food Thickener on Dissolution and Laxative Activity of Magnesium Oxide Tablets in Mice.

The present study examined the dissolution of magnesium oxide (MgO) from MgO tablets placed in a food thickening agent (food thickener) and its effects on laxative activity. We prepared mixtures of MgO tablets suspended in an aqueous suspension and food thickeners in order to evaluate the dissolution of MgO. The results of the dissolution tests revealed that agar-based food thickeners did not affect the MgO dissolution. In contrast, some xanthan gum-based food-thickener products show dissolution rates with certain mixtures containing disintegrated MgO tablets suspended in a food thickener that decrease over time. However, other xanthan gum-based food-thickener products show dissolution rates that decrease immediately after mixing, regardless of the time they were allowed to stand. In order to investigate the laxative activity of MgO, we orally administered a mixture of MgO suspension and food thickener to mice and observed their bowel movements. The animal experiments showed that when agar-based food thickeners were used, the laxative activity of MgO was not affected, but it decreased when xanthan gum-based food thickeners were used.

[Exploring effective components of laxative effect of Anemarrhenae Rhizoma based on Chinese herbal processing theory].

Anemarrhena asphodeloides processed by salt and raw product was compared including both chemical composition and laxative function in order to find the possible active substance to cure constipation. Processed and raw Anemarrhenae laxative effect on experimental constipation models was observed as well as chemical composition using UPLC-MS technology and the total sugar content was determined by phenol sulfuric acid method. Processed Anemarrhenae water extract improved excrement more than raw which has significant difference compared with the blank group (P < 0.05). On the other hand, the total ion flow spectrum showed no significant difference in most substance, but the total sugar content was significantly higher than raw product. Anemarrhenae ancient be recognized benefitting for draining body water in traditional Chinese medicine which has been lost in modern books because it is manifested as excellent laxative effect not diuretic effect. Saccharides carbohydrate may have closely relationship with this magically effect.

Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents.

BACKGROUND: The present study was aimed to provide ethnopharmacological basis for the medicinal use of Viola betonicifolia whole plant in indigestion and constipation. METHODS: Mice were used in in-vivo prokinetic and laxative studies while in-vitro experiments were conducted on isolated tissues of rabbit and guinea-pig gut preparations suspended in a tissue bath to measure isotonic contractions. RESULTS: The crude methanolic extract of Viola betonicifolia (VBME) showed partially atropine-sensitive prokinetic (50 and 100 mg/kg) and laxative (30 and 100 mg/kg) activities in mice. When tested in isolated rabbit jejunum and guinea-pig ileum, VBME caused dose-dependent contractions at 0.01-0.3 mg/mL and 0.03-5 mg/mL, respectively. The spasmogenic effect was partially sensitive to atropine, while the presence of pyrilamine, SB203186 or hexamethonium had no effect in both gut preparations. VBME partially inhibited acetylcholinesterase enzyme (19%) in the in-vitro assay. The spasmodic effect of VBME was more efficacious in guinea-pig ileum than rabbit jejunum preparation. The phytochemical analysis of the crude methanolic extract for total alkaloids and saponins revealed that the VBME is a rich source of alkaloids and saponins. CONCLUSIONS: This study showed the prokinetic and laxative effects of Viola betonicifolia in mice, partially mediated through cholinergic action. The in-vitro spasmodic effect of the plant extract was also partially sensitive to atropine indicating more than one mechanisms in the gut stimulant effect. This study provides a rationale for the medicinal use of Viola betonicifolia in indigestion and constipation.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

ETHNOPHARMACOLOGICAL RELEVANCE: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. AIM OF THE STUDY: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). MATERIALS AND METHODS: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. RESULTS: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. CONCLUSION: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

Clinical trial: marine lipid suppositories as laxatives.

UNLABELLED: Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. RESULTS: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). CONCLUSION: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials.

Gastrointestinal stimulant effect of Urginea indica Kunth. and involvement of muscarinic receptors.

Urginea indica Kunth. (Family; Liliaceae) was studied for its gastrointestinal stimulant effect to rationalize the traditional medicinal uses as a digestive aid, stomachic and laxative. The crude aqueous-methanol extract of Urginea indica bulb (Ui.Cr) was tested on mice and isolated gut preparations. Ui.Cr, which was tested positive for alkaloids, tannins and coumarins, increased faecal output and accelerated charcoal meal transit in mice (6-12 mg/kg, p.o.), similar to that caused by carbachol (10 mg/kg). Ui.Cr (0.01-1 mg/mL) caused a spasmogenic effect in guinea-pig ileum that was reproduced in rabbit jejunum (0.01-0.3 mg/mL) followed by relaxation at a higher concentration. Like carbachol, the stimulant effect of Ui.Cr was blocked by atropine, suggesting the activation of muscarinic receptors mediating the prokinetic effect. Ui.Cr (0.01-5.0 mg/mL) also inhibited K(+) (80 mm)-induced contraction in rabbit jejunum and shifted the Ca(2+) concentration-response curves to the right, similar to verapamil, a standard calcium channel blocker. These data, indicating the presence of a gastrointestinal stimulant effect in Urginea indica possibly mediated through a cholinergic mechanism, provide a rationale for the use of Urginea indica in indigestion and constipation. The presence of a calcium antagonist effect in the plant may help to alleviate untoward effects of the plant that may result from an excessive increase in gut motility.

Severe hyperphosphatemia after administration of sodium-phosphate containing laxatives in children: case series and systematic review of literature.

INTRODUCTION: Sodium phosphate-containing laxatives are commonly used as first-line treatment option for constipation in children and adolescents. Hyperphosphatemia is an infrequent, but potentially life-threatening complication of laxative application. METHODS: We report a case series of three children exhibiting severe hyperphosphatemia and hypocalcemia after utilization of sodium phosphate-containing laxatives, necessitating intensive care services in two of three cases. Additionally, we reviewed 32 case reports of similar occurrences. RESULTS: We identified 28 publications on the subject dating from 1968 to 2010. Mean age of all children in reports was 2.83 years; sex was approximately equally distributed. While 18 patients suffered from either pre-existing gastrointestinal comorbidity or other major systemic disease, no or only unrelated, minor conditions were present in ten children. One-third of patients received laxatives repeatedly before the incident. Findings associated with hyperphosphatemia include lethargy, dizziness, stiffness, tachypnea, tachycardia and severe dehydration in almost all cases, and tetany, carpopedal spasm, and prolonged QT interval in a subset. While about 80% of children recovered without residual findings, three deceased and one incurred persistent hypoxic brain damage. CONCLUSION: Physicians should be alerted to the possibility of phosphate toxicity in children and adolescents treated with laxatives.

Therapeutic effect of Moringa oleifera leaves on constipation mice based on pharmacodynamics and serum metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera is native to India, and has been introduced to China in recent years. Moringa oleifera leaves (MOL), as Ayurvedic medicine, has efficacy of Pachana karma (digestive) and Virechana karma (purgative). Folium Sennae (FS), Rhubarb (RB), Aloe vera (AV), Hemp seed (HS) are commonly used as laxatives in Traditional Chinese Medicine (TCM), which have different characteristics. However, the intensity of the diarrheal effect of MOL and its mechanism of action are unclear. AIM OF THE STUDY: The methods of pharmacology and omics were used to compare the purgative effects of MOL and FS, RB, AV, HS, and their effects on metabolomics, to analyze the purgative characteristics and related mechanisms of MOL. MATERIALS AND METHODS: C57BL/6J mouse model of constipation was established by feeding low-fiber food. Feces parameters and colon pathology were used to evaluate the effect of FS, RB, AV, HS and MOL. And mass spectrometry-based serum metabolomics was performed. The differential metabolites of these herbs in the treatment of constipation were obtained by OPLS-DA analysis. Furthermore, pathway analysis was conducted based on different metabolites. RESULTS: Moringa leaves can adjust the stool number, wet fecal weight and fecal water content to varying degrees to achieve laxative effects, and recover colon muscle thickness and mucus. Analysis of metabolomics results showed that 71 metabolites from LC-MS datasets between model group and control group were obtained. 29, 12, 44, 29 and 20 metabolites were significantly reversed by FS, RB, AV, HS, MOL compared with model group respectively. According to the metabolic pathways, RB and AV may be clustered into a similar category, and MOL, FS and HS showed similarity of metabolic characteristics. CONCLUSION: The purgative effect of MOL is inferior to that of FS, and stronger than that of AV, RB and HS. The metabolic pathway for constipation is more similar to that of FS. MOL has a long-lasting and mild effect of laxative, increasing defecation volume and water content of feces, and may become a fewer side effects medicine to treat constipation.

CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives.

AIM: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants. METHODS: A cell-based fluorescent assay to measure I(-) influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl(-) current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo. RESULTS: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated I(-) influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay, the three compound enhanced Cl(-) currents in epithelia formed by CFTR-expressing FRT cells with EC(50) values of 73 ± 1.4, 56 ± 1.7, and 50 ± 0.5 µmol/L, respectively, and Rhein also enhanced Cl(-) current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTR(inh)-172. In in vivo closed loop experiments, rhein 2 mmol/L stimulated colonic fluid accumulation that was largely blocked by CFTR(inh)-172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity. CONCLUSION: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs.