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The effects of extracts from anti-diarrheic Thai medicinal plants on the in vitro growth of the intestinal protozoa parasite: Blastocystis hominis.

The activities of n-hexane, dichloromethane and methanol extracts from five anti-diarrheic Thai medicinal plants, Acacia catechu (Fabaceae) resin, Amaranthus spinosus (Amaranthaceae) whole plant, Brucea javanica (Simaroubaceae) seed, Piper longum (Piperaceae) fruit and Quercus infectoria (Fagaceae) nut gall were tested against the in vitro growth of fresh isolates of the intestinal protozoan parasite, Blastocystis hominis. The extracts at concentrations that ranged from 62.5 to 2000 microg/mL, were incubated with several isolates of Blastocystis hominis for 48 h. The activities were classified as killed, inhibited, moderately inhibited and not-inhibited. Dichloromethane and methanol extracts from the Brucea javanica seed and a methanol extract from Quercus infectoria nut gall showed the highest activity. At a concentration of 2000 microg/mL, the three extracts killed 82, 75 and 67% of the Blastocystis hominis samples tested and inhibited 94, 100 and 76% of them, respectively. Metronidazole, used as a reference antiprotozoan drug, at a concentration of 40 microg/mL, killed 97% of the Blastocystis hominis isolates and inhibited all samples tested at concentrations that ranged from 1.25 to 20 microg/mL.

Animals↗

Effects of wild ginseng (Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats.

The aim of this study was to examine the possible antioxidant activities of wild Panax ginseng leaf extract intake in streptozotocin (STZ)-induced diabetic rats (WGLE). Initial blood glucose levels increased abruptly after streptozotocin injection. After 4 weeks of WGLE supplementation, blood glucose levels were lower in animals fed 40 mg/kg (266 mg/dL) and 200 mg/kg (239 mg/dL) than those in no-WGLE fed diabetic rats (464 mg/dL). The concentration of blood TBARS, which are considered the main products of glucose oxidation in blood, was also lowered by WGLE supplementation. These results indicate that WGLE supplementation is involved in suppressing a sudden increase in blood glucose levels and a consequent decrease in TBARS levels in diabetic rats. TBARS levels in the liver, kidney and spleen of WGLE-fed diabetic groups were also significantly lower than in the control diabetic group indicating that oral administration of WGLE effectively suppresses lipid peroxidation that occurs in the organs of diabetic rats. Antioxidant activities of WGLE supplementation further extend in suppressing activities of antioxidant related enzymes, such as glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), in organs of diabetic rats. These results confirm the effectiveness of WGLE supplementation in detoxifying free radicals that are produced excessively in diabetic-induced complications.

Animals↗

Anti-diarrhoeal and ulcer-protective effects of the aqueous root extract of Guiera senegalensis in rodents.

The anti-diarrhoeal and ulcer-protective properties of the aqueous root extract of Guiera senegalensis, a popular herbal traditional medicine in Nigeria were investigated in rats and mice. Acute toxicity studies were also carried out. The intestinal transit in mice was significantly (P < 0.05) reduced and gastric emptying delayed. One hundred and Two hundred milligrams per kilogram (p.o.) of the extract elicited a greater anti-motility activity than 0.1 mg/kg of atropine. The extract exhibited ulcer-protective properties against ethanol-induced ulceration in rats with maximal anti-ulcer activity recorded at 100 mg/kg. Guiera senegalensis also exerted significant anti-enteropooling effects causing a dose-related inhibitory effect on castor oil-induced enteropooling in rats. A profound anti-diarrhoeal activity was observed when Guiera senegalensis was tested in diarrhoeic mice. The frequency of defaecation as well as the wetness of the faecal droppings was significantly reduced. Furthermore, the extract produced 100% inhibition of castor oil-induced diarrhoea in mice. The oral LD50 values obtained were > 5000 mg/kg in both mice and rats. The results support the folkloric applications of Guiera senegalensis for the treatment of diarrhoea and ulcer in Nigerian herbal traditional medicine.

Animals↗

Preliminary pharmacological studies on Piper chaba stem bark.

Piper chaba Hunter (Piperaceae) is a common pepper in the southern part of Bangladesh. Various parts of this plant have been extensively used in different traditional formulations including ayurveda. In order to rationalize the ethnomedical uses of this plant in a number of ailments, the methanol extract of the stem bark was subjected to preliminary evaluation for analgesic, anti-inflammatory, diuretic, anti-diarrhoeal, effect on gastrointestinal motility and CNS depressant activity in mice and rat at 125, 250 and 500 mg/kg body weight doses. The extract at given doses significantly and dose dependently reduced the frequency of acetic acid induced writhing in mice, prolonged the tail flicking latency in mice, reduced Carrageenan-induced paw edema volume in rat, delayed the onset as well as reduced the frequency of castor oil induced diarrhoeal episodes in mice, decreased gastrointestinal motility as assessed by the charcoal motility test in mice and prolonged pentobarbitone induced sleeping time in mice. However at the same doses, the extract exhibited moderate diuretic activity only at the highest dose.

Acetic Acid↗

Antidiarrhoeal activity of the methanol extract of the barks of Xylocarpus moluccensis in castor oil- and magnesium sulphate-induced diarrhoea models in mice.

The methanol (MeOH) extract of the barks of Xylocarpus moluccensis, and different fractions of this extract were studied for antidiarrhoeal activity using castor oil- and magnesium sulphate-induced diarrhoea models in mice. At the doses of 250 and 500 mg/kg, the MeOH extract showed significant antidiarrhoeal activity in both models. The EtOAc fraction (EAF) and the residual MeOH fraction (RMF) exhibited similar activity using a dose of 250 mg/kg in both models. No antidiarrhoeal activity was observed with the chloroform fraction (CHF) at the test doses. When tested for antibacterial effect, the MeOH extract displayed moderate inhibitory activity against Escherichia coli, Vibrio cholera, Staphylococcus aureus, Staphylococcus epidermis, Shigella dysentery, Staphylococcus pyogenes, Salmonella typhi, Pseudomonas aeruginosa and Enterobacter aerogenes. While the CHF inhibited the growth of Escherichia coli, Vibrio cholerae, Shigella dysenteriae, Shigella sonnei, Staphylococcus epidermis, Staphylococcus pyogenes and Pseudomonas aeruginosa, the EAF was active against all test organisms except Vibrio cholera and Staphylococcus epidermis. The RMF inhibited the growth of all the test organisms with moderate zone of inhibition. On the basis of these findings, it can be assumed that Xylocarpus moluccensis could be a potential source for novel 'lead' discovery for antidiarrhoeal drug development.

Animals↗

Antidiarrhoeal activity of ethanol extract of the bark of Dalbergia lanceolaria.

The bark of Dalbergia lanceolaria was undertaken for evaluation of antidiarrhoeal activity in albino mice based on ethnobotanical lead. This bark was collected from Khanapur area of Western Ghats near Pune, Maharashtra, India. The successive solvent extraction of bark was carried out after drying, using petroleum ether (60-80 degrees C) and ethanol in soxhlet apparatus. The ethanol extract showed activity against castor oil, magnesium sulphate induced diarrhoea in albino mice. The extract was also studied for castor oil induced intraluminal fluid accumulation as well as charcoal transit in normal and barium chloride treated animals. The extract reduced significantly intraluminal fluid accumulation and intestinal motility.

Animals↗

Anti-diarrheal effect of Galla Chinensis on the Escherichia coli heat-labile enterotoxin and ganglioside interaction.

Enterotoxigenic Escherichia coli (ETEC) is the most frequently isolated enteropathogen, accounting for approximately 210 million diarrhea episodes annually. ETEC-induced diarrhea is initiated by the binding of B subunit of heat-labile enterotoxin (LTB) to the ganglioside G(M1) on the surface of intestinal epithelial cell. Therefore, we evaluated the inhibitory effects of 297 Chinese medicinal herbs on the LTB and G(M1) interaction by G(M1)-enzyme-linked immunosorbent assay. Galla Chinensis extract (GCE) exhibited anti-LT-induced diarrheal effect in the patent mouse gut assay, with IC50 value of 4.7+/-1.3 mg/ml. GCE also inhibited the binding of LTB to G(M1), suggesting that GCE suppressed the LT-induced fluid accumulation by blocking the binding of LTB to G(M1). Furthermore, the ethyl acetate (EA) soluble fraction was the most active fraction of Galla Chinensis that inhibiting the binding of LTB to G(M1) with an IC50 value of 153.6+/-3.4 microg/ml. The major components of the EA fraction should be phenolic derivatives according to a thin-layer chromatography analysis. Gallic acid, the major component of EA fraction, blocked the binding of LTB to G(M1), resulting in the suppression of LT-induced diarrhea. In conclusion, these data suggested that Galla Chinensis and gallic acid might be potent drugs for the treatment of LT-induced diarrhea.

Animals↗

Pharmacological studies of anti-diarrhoeal activity of Gentianopsis paludosa.

The pharmacological studies of anti-diarrhoeal activity of Gentianopsis paludosa were carried out. The 75% ethanol extract (100-400 mg/kg) of Gentianopsis paludosa inhibited castor oil-induced diarrhoea and also reduced gastrointestinal motility in the charcoal meal test in mice. In the rabbit-isolated ileum, the extract showed inhibitory effects not only on its spontaneous contraction, but also on acetylcholine (Ach, 0.1 mM)- and KCl (60 mM)-induced contractions. Furthermore, the ethanol extract (0.4-0.6 mg/ml) shifted the CaCl2 dose-effect curves to the right in a non-competitive manner and significantly reduced the acetylcholine-induced contraction of isolated ileum in Ca2+-free solution like verapamil (0.1 mM), which suggest that the extract interferes with Ca2+ movement. These results support the traditional use of Gentianopsis paludosa in the treatment of diarrhoea.

Acetylcholine↗

Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn. (Rubiaceae).

Paederia foetida L. is used as a remedy for diarrhoea and dysentery in Asia, but has not been investigated for its antidiarrhoeal properties. Antidiarrhoeal activity of 90% ethanol extract of Paederia foetida was investigated in this study using castor oil and magnesium sulphate-induced diarrhoea models in mice. The extract significantly increased the latent period of diarrhoea in both the models. In the castor oil study, the purging index (PI) value lowered in 1 h of the study at (100, 250 and 500 mg/kg) doses. The effect continued up to 6-h period only at 500 mg/kg dose. The plant notably reduced the purging index value in a dose-dependent manner in magnesium sulphate-induced diarrhoea. Paederia foetida, in general, reduced the gastrointestinal motility with barium sulphate milk both in 15- and 30-min time intervals. The extract significantly decreased the cisplatin-induced gastrointestinal motility at all doses at both time intervals. The extract also enhanced the morphine-induced reduction of motility at 500 mg/kg dose level at both time intervals. The results suggest that Paederia foetida showed antidiarrhoeal activity by inhibiting intestinal motility and justify its use in traditional medicine.

Animals↗

Phytochemical composition of essential oil from seeds of Zingiber roseum Rosc. and its antispasmodic activity in rat duodenum.

A combination of GC and GC-MS revealed the presence of 60 compounds out of which 47 compounds (96.2% of the oil) were identified in the essential oil of seeds of Zingiber roseum Rosc., the major compounds being alpha-pinene, beta-pinene, limonene, p-cymene, alpha-terpineol and verticiole. The unique feature is the dominant presence of mono- and sesquiterpene hydrocarbons which make about 82% of the oil. The oil showed myorelaxant activity on isolated rat duodenal smooth muscle. The Zingiber roseum seed essential oil (ZRSEO) relaxed both cabachol- and KCl-induced contractile responses with IC(50) of non-significant difference. The results confirm a common mechanism in both the types of action of ZRSEO and suggests a probable inhibitory effect of ZRSEO on influx of Ca(2+) through cell membrane of rat duodenal smooth muscle.

Animals↗

Inhibition of intestinal motility and secretion by extracts of Epilobium spp. in mice.

Ethanol extracts of the fresh aerial parts of various Epilobium species were tested to elucidate the mechanism of their gastrointestinal activity in animals. The methods of charcoal meal, castor oil-induced diarrhoea, and enteropooling assay were used to evaluate their effect on mouse gut at various dose levels. The extracts were found to have a significant activity in all models. Moreover, the extracts resulted to possess very little toxicity. Thus, it can be concluded that Epilobium possesses anti-diarrhoeal, anti-motility, and anti-secretory activities and can prove beneficial in the treatment of gastrointestinal disorders.

Animals↗

Evaluation of the antidiarrhoeal activity of Byrsocarpus coccineus.

Based on its use in traditional African medicine, the antidiarrhoeal activity of the aqueous leaf extract of Byrsocarpus coccineus, Connaraceae, was evaluated on normal and castor oil-induced intestinal transit, castor oil-induced diarrhoea, enteropooling and gastric emptying. The extract (50, 100, 200 and 400 mg/kg, p.o.) produced a significant (P<0.05) dose dependent decrease in propulsion in the castor oil-induced intestinal transit in mice. The mean peristaltic index (%) for these doses of extract, control (distilled water; 10 ml/kg, p.o.) and morphine (10 mg/kg, s.c.) were 55.27+/-1.86, 53.12+/-3.73, 38.60+/-3.79, 30.25+/-1.27, 89.33+/-5.62 and 20.29+/-3.38, respectively. The effect of the extract at the highest dose was significantly (P<0.05) lower than that of the standard drug. This effect was antagonised by yohimbine (1 mg/kg, s.c.) but not by isosorbide dinitrate (IDN, 150 mg/kg, p.o.). At 200 mg/kg, the extract produced a significant decrease in propulsion in normal intestinal transit. In a dose dependent manner, it delayed the onset of diarrhoea, produced a significant decrease in the frequency of defaecation, severity of diarrhoea and protected the mice treated with castor oil. Mean diarrhoea scores were 30.83+/-1.72, 22.40+/-1.71, 21.43+/-1.32, 13.80+/-0.33, 18.00+/-3.94 and 7.67+/-2.41 for control, extract (50, 100, 200 and 400 mg/kg) and morphine, respectively. This effect was not antagonized by IDN. The extract (400 mg/kg) significantly decreased the volume (ml) of intestinal fluid secretion induced by castor oil (0.60+/-0.23) compared with 1.27+/-0.12 for control. However, there was no significant effect on gastric emptying. The results obtained suggest that Byrsocarpus coccineus possesses antidiarrhoeal activity due to its inhibitory effect on gastrointestinal propulsion, mediated through alpha(2) adrenoceptors, and also inhibition of fluid secretion. Preliminary phytochemical analysis revealed the presence of alkaloids, tannins, saponins, reducing sugars, glycosides and anthraquinones.

Animals↗

Preliminary pharmacological screening of Bixa orellana L. leaves.

Preliminary pharmacological studies were performed on the methanol extract of Bixa orellana L. (Bixaceae) leaves to investigate neuropharmacological, anticonvulsant, analgesic, antidiarrhoeal activity and effect on gastrointestinal motility. All studies were conducted in mice using doses of 125, 250 and 500 mg/kg of body weight. In the pentobarbitone-induced hypnosis test, the extract statistically reduced the time for the onset of sleep at 500 mg/kg dose and (dose-dependently) increased the total sleeping time at 250 and 500 mg/kg dose. A statistically significant decrease in locomotor activity was observed at all doses in the open-field and hole-cross tests. In the strychnine-induced anticonvulsant test, the extract increased the average survival time of the test animals (statistically significant at 250 and 500 mg/kg). The extract significantly and dose-dependently reduced the writhing reflex in the acetic acid-induced writhing test. Antidiarrhoeal activity was supported by a statistically significant decrease in the total number of stools (including wet stools) in castor oil-induced diarrhoea model. A statistically significant delay in the passage of charcoal meal was observed at 500 mg/kg in the gastrointestinal motility test. The extract was further evaluated in vitro for antioxidant and antibacterial activity. It revealed radical scavenging properties in the DPPH assay (IC(50)=22.36 microg/ml) and antibacterial activity against selected causative agents of diarrhoea and dysentery, including Shigella dysenteriae.

Acetic Acid↗

Assessment of antidiarrhoeal activity of the methanol extract of Xylocarpus granatum bark in mice model.

The methanol extract of Xylocarpus granatum bark was studied for its antidiarrhoeal properties in experimental diarrhoea, induced by castor oil and magnesium sulphate in mice. At the doses of 250 and 500 mg/kg per oral, the methanol extract showed significant and dose-dependent antidiarrhoeal activity in both models. The extracts also significantly reduced the intestinal transit in charcoal meal test when compared to atropine sulphate (5 mg/kg; i.m.). The results showed that the extracts of Xylocarpus granatum bark have a significant antidiarrhoeal activity and supports its traditional uses in herbal medicine.

Animals↗

Application of a new electrolyte circulation method for the ex situ electrokinetic bioremediation of a laboratory-prepared pentadecane contaminated kaolinite.

Ex situ electrokinetic (EK) bioremediation of a laboratory-prepared pentadecane-contaminated kaolinite was carried out. Extraneous bacteria and ionic nutrients were continuously supplied to the soil specimen by a new electrolyte circulation method, which controlled electrical pH change of electrolyte solution to keep bacterial activity. During the EK bioremediation the anode region showed the highest colony forming unit (CFU) due to electrical attraction between anode and bacteria. Simultaneous increases of CFU and uniform pentadecane removal in most soil regions demonstrated that electro-osmosis as well as electrophoresis affected the bacterial transport in soil. At 3.13 mA/cm2, increase in soil temperature to above 45 degrees C inhibited bacterial activity, which caused the decrease of removal efficiency. The removal amount of pentadecane increased with initial pentadecane concentration at the same current densities (0.63 and 1.88 mA/cm2) because of the increased amount of weakly bound pentadecane onto the soil surface. The highest removal efficiency (77.6%) was obtained at 0.63 mA/cm2 for 1000 mg/kg pentadecane after 14 days. Consequently, the present methods of EK bioremediation demonstrated superiority over the conventional bioremediation, which had inherent demerits of slow degradation and low removal efficiency.

Alkanes↗

LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsule in human volunteers.

The purpose of the present study was to develop a standard protocol for loperamide hydrochloride bioequivalence testing. For this purpose, a simple rapid and selective LC-MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of loperamide hydrochloride in human plasma, and we followed this with a bioavailability study. Methyl tert-butylether (MTBE) was used to extract loperamide hydrochloride and ketoconazole (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a Zorbax RX C18 column (5 microm, 2.1 mm x 150 mm) using acetonitrile-water-formic acid (50:50:0.1 (v/v)) as a mobile phase. The retention times of loperamide hydrochloride and IS were 1.2 and 0.8 min, respectively. Quadrupole MS detection was by monitoring at m/z 477 (M + 1) corresponding to loperamide hydrochloride and at m/z 531 (M + 1) for IS. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of loperamide hydrochloride was evaluated in eight healthy male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of four 2mg capsules of loperamide: the area under the plasma concentration versus time curve from time 0 to 72 h (AUC72 h) 19.26 +/- 7.79 ng h/ml; peak plasma concentration (Cmax) 1.18 +/- 0.37 ng/ml; time to Cmax (Tmax) 5.38 +/- 0.74 h; and elimination half-life (t1/2) 11.35 +/- 2.06 h. The developed method was successfully used to study the bioavailability of a low dose (8 mg) of loperamide hydrochloride.

Adult↗

Weekly administration of irinotecan (CPT-11) plus cisplatin for refractory or relapsed small cell lung cancer.

PURPOSE: Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer. METHODS: Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water. RESULTS: Twenty-five patients who had prior treatments of etoposide and platinum containing regimens (16 refractory patients and nine relapsed patients) were entered. The mean dose-intensities of CPT-11 and cisplatin were 154.8 and 77.4 mg/m(2) per course, respectively. Therefore, 86% of the planned dose was delivered. There were 20 partial responses and an overall response rate of 80% (95% confidence interval, 62-96%) was obtained. The median time to progression and the median survival after starting this regimen were 3.6 and 7.9 months, respectively. The major toxicity was myelosuppression. Grades 3 and 4 neutropenia occurred in 24 and 12% of patients, respectively. One patient with febrile neutropenia was experienced, and Grade 3 diarrhea was observed in 8%. But there was no treatment death. CONCLUSION: Weekly administrations of CPT-11 plus cisplatin together with Oral Alkalization and Control of Defecation provide a practical and well tolerated regimen that was active for refractory or relapsed small cell lung cancer.

Aged↗

High-methoxyl pectin has greater enhancing effect on glucose uptake in intestinal perfused rats.

OBJECTIVE: Pectins have been known to decrease blood glucose levels. However, the mechanism of this effect is unclear. The direct action of various pectins (high- or low-methoxyl pectins) on the intestinal absorption of glucose was investigated in gut-perfused rats. METHODS: After equilibrium, jejunal and ileal segments were simultaneously perfused with an isotonic electrolyte solution (pH 7.4) containing glucose (10 mM/L) and high- or low-methoxyl pectins (10 g/L). Each test or control solution was perfused in a random sequence, with perfusion times of 30 min. Changes in glucose concentration of perfusate solution reservoir were determined over the experimental period. RESULTS: High- and low-methoxyl pectins in the perfusate significantly inhibited jejunal uptake of glucose compared with the control (P < 0.05). High-methoxyl pectins had greater inhibitive effect on intestinal absorption of glucose than low-methoxyl pectins. The observed changes in glucose and water absorptions caused by high- or low-methoxyl pectins were reversible by switching to a pectin-free perfusate. In addition, net water absorption changed to secretion after addition of high- or low-methoxyl pectins. CONCLUSIONS: These results suggest that the decrease in intestinal absorption of glucose observed after perfusion of high- or low-methoxyl pectins may be caused by viscosity-related increases in mucosal unstirred layer thickness.

Animals↗