Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sennosides”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

Chronic sennoside treatment does not cause habituation and secondary hyperaldosteronism in rats.

Rats were treated with sennosides (6 x 10, 6 x 40 or 2 x 30 mg/kg weekly) or with danthron (6 x 500 mg/kg weekly) for 6 months. The laxative effect as measured by faecal wet weight during the first 10 h after treatment increased 3- to 4-fold by the higher sennoside doses (daily or intermittently) and 1- to 3-fold by danthron. The low sennoside dose had no measurable effect except on the 1st day (2 fold) compared with the control group. Mean faecal water content increased from 53% (controls) to 66-79% in rats treated with high sennoside doses and to 57 (1st day) -69% in danthron-treated rats. Serum aldosterone levels and mucosal Na(+)-K(+)-ATPase activities in the small intestine and colon did not change with treatment. There were no signs of habituation or secondary hyperaldosteronism due to sennosides or danthron in spite of chronic diarrhoea over 6 months.

Aldosterone↗

The effect of sennosides on colonic mucosal histology and bowel preparation.

INTRODUCTION: A single high dose of sennosides is often used to optimize bowel preparation for diagnostic procedures. From previous studies it is suspected that sennosides in such a dose cause acute damage to the colonic mucosa. This study was designed to determine any effects of sennosides on histology of colonic mucosa and on bowel preparation. RESULTS: In a prospective study 171 patients were randomized for bowel preparation. 84 patients received 1 ml/kg (maximal 75 ml) of a syrup containing 2.0 mg/ml sennoside A and B and 3-5 l of a lavage solution (Sen), 87 patients only received 3-5 l lavage solution (NSen). All patients completed a questionnaire on which patient tolerance was scored. Another questionnaire was completed by the endoscopist, recording quality of the preparation. From the 40 patients with a normal colon (19 Sen, 21 NSen) a biopsy was taken from the sigmoid colon and analyzed for morphological abnormalities. No difference could be demonstrated in tolerance or quality of bowel preparation between the two groups. A marked increase of mononuclear infiltrate in the lamina propria was observed in Sen compared to NSen: in 10/19 vs. 2/21 patients respectively, p < 0.0005. CONCLUSION: As these microscopic effects could hamper the interpretation of colonic biopsies, bowel preparation without sennosides is to be recommended.

Adolescent↗

Metabolic activation of sennoside C in mice: synergistic action of anthrones.

Sennosides A and C directly injected into the caecum of mice showed equal purgative activity. Intracaecal administration reduced time to onset of diarrhoea induced by sennoside C from about 3 h after oral administration to about 24 min. At 2.3 h after oral administration of sennoside C, nearly equimolar amounts of aloe-emodin anthrone and rhein anthrone were detected in the large intestine of mice. The purgative effect of oral sennoside C could be reduced by pretreating mice with chloramphenicol. This was observed as a decreased formation of total anthrones in the large intestine. Both anthrones and an equimolar mixture of both anthrones directly injected into the caecum exerted a purgative effect, although the activity was lower for aloe-emodin anthrone. The intracaecal ED50 values were 54.5 (24.1-89.6), 11.4 (5.0-15.7) and 11.2 (6.1-14.6) mumol kg-1 for aloe-emodin anthrone, rhein anthrone and an equimolar mixture of both anthrones, respectively. We concluded that aloe-emodin anthrone and rhein anthrone, formed mainly by intraluminal bacterial action, are the true active metabolites of sennoside C in mice and that both anthrones synergistically exert their purgative effects on mice.

Animals↗

Development of a one-step immunochromatographic strip test for the detection of sennosides A and B.

An immunochromatographic strip test was developed to detect sennoside A (1) and sennoside B (2) using anti-1 and anti-2 monoclonal antibodies. The qualitative assay was based on a competitive immunoassay in which the detector reagent consisted of colloidal gold particles coated with the respective sennoside antibodies. The capture reagents were 1- and 2-human serum albumin (HSA) conjugates immobilised on a nitrocellulose membrane on the test strip. The sample containing 1 and 2, together with detector reagent, passed over the zone where the capture reagents had been immobilised. The analytes in the sample competed for binding to the limited amount of antibodies in the detector reagent with the immobilised 1- and 2-HSA conjugates on the membrane and hence positive samples showed no colour in the capture spot zone. Detection limits for the strip test were 125 ng/mL for both sennosides. The assay system is useful as a rapid and simple screening method for the detection of 1 and 2 in plants, drugs and body fluids.

Anthraquinones↗

Effects of sennosides on colonic myoelectrical activity in man.

The effects of sennosides on colonic myoelectrical activity were investigated in man. Spiking activity of the left and sigmoid colons was continuously recorded in seven constipated patients during two sessions from 5:00 PM to 9:00 AM. Each patient received orally at 7:00 PM on two consecutive days 30 mg of sennosides one day (sequence S) and placebo on the other (sequence P) in a random fashion. A significant (P less than 0.05) increase of peristaltic activity (migrating long spike bursts or MLSBs) after sennosides was observed between 1:00 and 7:00 AM, and a corresponding decrease between 7:00 and 9:00 AM. No change was noted in total short spike burst (SSB) activity or in SSBs characteristic of the rectosigmoid area. This study indicates that the main modification of colonic motility induced by sennosides was a stimulation of propulsive activity (MLSBs), which occurred between 6-12 hr after oral administration, the delay required for orocecal transit and metabolism of the drug.

Action Potentials↗

Validated HPLC method for determination of sennosides A and B in senna tablets.

This study developed an efficient and reliable ion-pair liquid chromatographic method for quantitation of sennosides A and B in commercial senna tablets. Separation was conducted on a Hypersil C 18 column (250 x 4.6 mm, 5 microm) at a temperature of 40 degrees C, using a mixture of 0.1 M acetate buffer (pH 6.0) and acetonitrile (70:30, v/v) containing 5 mM tetrahexylammonium bromide as mobile phase. Sennosides A and B were completely separated from other constituents within 14 min. The developed method was validated. Both run-to-run repeatability (n=10) and day-to-day reproducibility (n=3) of peak area were below 0.4% RSD. Linearity of peak area was tested in the range 30-70 microg/ml (r>0.9997). Accuracy was assessed with recovery and the recoveries for sennosides A and B were 101.73+/-1.30% and 101.81+/-2.18% (n=3 x 6), respectively. Robustness of the analytical method was tested using a three-leveled Plackett-Burman design in which 11 factors were assessed with 23 experiments. Eight factors (column, concentration of ion pair reagent, % of organic modifier (acetonitrile), buffer pH, column temperature, flow rate, time constant and detection wavelength) were investigated in a specified range above and below the nominal method conditions. It was found that: (1) column and % acetonitrile affected significantly resolution and retention time, (2) column, % acetonitrile, column temperature, flow rate and time constant affected significantly the plate number of sennoside A, and (3) column and time constant affected significantly the tailing factor.

Anthraquinones↗

The effect of sennosides on bacterial translocation and survival in a model of acute hemorrhagic pancreatitis.

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Acute Disease↗

Effect of sennosides on colon motility in dogs.

Oral administration of sennosides (20-30 mg/kg) to fasted dogs has been shown to induce a strong and long-lasting inhibition of myoelectric colon activity which was evident after a delay of 6-10 h corresponding to oro-cecal transit and colonic metabolism and was accompanied by abundant diarrhea. When sennosides were given 1 h before a meal, the postprandial increase in colon motility failed to appear. Recent studies with strain gage transducers confirm the inhibition of colonic motility after oral sennosides but, in addition, 3-10 'giant contractions' with a high amplitude appeared during the period of inhibition. Most of these single contractions were propagated over the second half of the colon at a velocity of 0.5-2 cm/min. Elimination of liquid feces was always associated with giant contractions. These giant contractions have also been described with other stimuli (i.v. guanethidine or neostigmine, oral castor oil, intraluminal hypertonic glucose) and are therefore not specific for sennosides.

Animals↗

Effect of sennosides and related compounds on intestinal transit in the rat.

The effect of pure sennosides A + B on large intestinal transit (LIT) was investigated in the rat. LIT was defined as the time from intracecal administration of a color marker through a chronically implanted catheter until first appearance of colored feces. Sennosides (50 mg/kg, administered orally 2-24 h before the marker) reduced LIT from greater than 6 h in controls to a minimum of 30-20 min after a 4- or 6-hour pretreatment. Longer pretreatment times increased LIT again reaching normal values after 24 h. Intracecal administration of sennosides and their natural metabolites (sennidins A + B, rhein-9-anthrone, rhein) simultaneously with the marker accelerated LIT to approximately 50-70 min. The laxative effect was less pronounced after rhein compared with the other compounds. Indometacin, loperamide, and calcium-channel antagonists (verapamil, nifedipine) partially antagonized the effect of intracecal sennosides on LIT and delayed, but did not suppress, appearance of soft feces.

Animals↗

Toxic effects of sennosides in laboratory animals and in vitro.

Sennosides were tested in a wide range of toxicity studies to evaluate risk assessment. From acute studies, sennosides could be classified as only slightly toxic in rats and mice after a single oral dose. The LD50 values were about 5,000 mg/kg in both species. The cause of death was probably due to an extensive loss of water and electrolytes following massive diarrhoea. In subacute studies with rats (max. 20 mg/kg) and dogs (max. 500 mg/kg), sennosides caused no specific local or systemic toxicity. Minor increase in kidney weight in rats was toxicologically not relevant. In a 6-month study with rats, sennosides were tolerated without specific toxic effects in doses up to 100 mg/kg. Effects on food consumption, body weight gain and some biochemical parameters as well as slight renal lesions can be interpreted as secondary effects following chronic diarrhoea. Mutagenicity tests and reproduction toxicity studies showed no abnormal results.

Animals↗

Long-term mucosal alterations by sennosides and related compounds.

Sennosides and related compounds are presumed to be severe cell poisons after prolonged ingestion. Some histological and ultrastructural studies in animals and man with such laxative misuse have revealed myenteric plexus and colonic epithelium injuries; but others have failed to point out identical data. In a first histological and ultrastructural study in mouse, we were unable to find any intestinal mucosa injury after long-term sennoside ingestion. In a second long-term experiment, we compared the effects of sennosides and 1,8-dihydroxyanthraquinone (synthetic anthracene derivative) on the mouse jejunum and colon. Electron microscopic observations showed nervous myenteric plexus abnormalities only in 1,8-dihydroxyanthraquinone-treated animals. These results suggest that sennosides have a good intestinal mucosa tolerance as opposed to aglycosidic-related compounds.

Animals↗

Sennoside-induced secretion and its relevance for the laxative effect.

The effect of oral treatment with sennosides (50 mg/kg) on the time-course of net H2O and electrolyte transport rates was studied in 1-hour incubation experiments in the rat colon in vivo. Net H2O, Na+ and Cl- absorption rates did not change during the first 4 h after treatment, but were reversed to net secretion after 6 h and partly recovered during the next 18 h. K+ and Ca2+ were secreted in controls, and net secretion increased from 6 to 24 h after treatment. Paracellular permeability of [14C]erythritol was 3-fold 6 h after treatment but unchanged at other times after treatment (2, 4, 12 or 24 h). LDH leakage into the lumen was not enhanced by treatment. Neither mucosal Na+, K(+)-ATPase activity nor cAMP or phosphodiesterase activity was affected by sennosides. As stool consistency and acceleration of transit by sennosides has entirely normalized 24 h after treatment but not net absorption of H2O and electrolytes, it is concluded that there may be regional differences in the absorptive behavior of the colon induced by sennosides. Slow transit and increased absorption in some parts of the colon may overcome secretion in other parts.

Animals↗

Purification and characterization of a novel sennoside-hydrolyzing beta-glucosidase from Bifidobacterium sp. strain SEN, a human intestinal anaerobe.

A novel beta-glucosidase, which is inducible and capable of catalyzing the hydrolysis of sennosides, was purified from Bifidobacterium sp. strain SEN with Triton X-100 solubilization and DEAE-cellulose column chromatography, by which hydrolytic activities toward sennoside B, 4-methylumbelliferyl beta-glucoside (MUG), and p-nitrophenyl beta-glucoside (pNPG) were obtained together in the same eluted fractions. The activity was stable against detergents such as sodium dodecyl sulfate (SDS) and Triton X-100, but was denatured by SDS and beta-mercaptoethanal when heated. The final preparation was shown to be nearly homogeneous on SDS-polyacrylamide gel electrophoresis (PAGE) either after the enzyme was denatured or when it was not denatured. In the non-denaturing SDS-PAGE, a single protein band hydrolyzed MUG on the gel. In the denaturing SDS-PAGE, the subunit mass of the enzyme was estimated to be 110 kDa. The enzyme was optimally active at pH 6.0 for hydrolysis of sennoside B and MUG. Km values for sennoside B and MUG are 0.94 and 0.53 mM, respectively. The enzyme also catalyzed the hydrolysis of pNPG, amygdalin, geniposide and salicin. It was less active against methyl beta-glucoside and incapable of hydrolyzing cellobiose. The beta-glucosidase activity was inhibited by deoxynojirimycin and p-chloromercuribenzenesulfonic acid, but was less susceptible to several metals (FeSO4, ZnCl2, and CuSO4), and 5,5'-dithio-bis(2-nitrobenzoic acid).

Anthraquinones↗

The influence of the sennosides on absorption of glycyrrhetic acid in rats.

In the course of our clinical studies of Kampo medicine (traditional Japanese medicines), we observed the pharmacokinetic interactions between two herbs. When Onpito (TJ-8117, Kampo medicine) containing licorice and rhubarb was administered orally to human subjects, we observed that the AUC(0-lim) and Cmax of glycyrrhetic acid (GA) in plasma were lower than those treated with other Kampo medicines containing licorice. In this study, we demonstrate the pharmacokinetic interactions of GA derived from glycyrrhizinic acid (GL) in licorice and anthraquinones derived from rhubarb. To our knowledge, this is the first report to investigate the pharmacokinetic interactions between two herbs. When GL was orally co-administrated to rats with a non-effective dose of sennoside A having purgative activity, the AUC(0-lim) and Cmax of GA decreased. In addition, sennoside A did not affect the metabolism of GL by the intestinal bacteria in vitro. In the examination using an in situ loop of rat colon, the remaining ratio of GA rose drastically by the co-administration of sennoside A, sennidin A and rhein. Observed inhibition activity of these anthraquinones on GA absorption depended on the concentration of the components added. The maximum inhibition ratio was approximately 75% by rhein, 60% by sennoside A and 25% by sennidin A. We conclude that the decrease of the pharmacokinetic parameters of GA in human plasma observed in the clinical study of TJ-8117 is attributable to an interactive action of absorption from the intestinal tract by anthraquinones contained in or derived from rhubarb.

Animals↗

The sennoside constituents of rhei rhizoma and sennae folium as inhibitors of serum monoamine oxidase.

Four (in total) compounds with inhibitory effects on the activity of bovine serum monoamine oxidase were isolated from the methanol-water extracts of Rhei Rhizoma (Daiou) and Sennae Folium (Senna), and identified as sennosides A, B, E and F. Among them, sennosides A and B were obtained from both Rhei Rhizoma and Sennae Folium, while sennosides E and F were detected only in the former. The 50% inhibitory concentrations of the four sennosides were 17, 9, 24 and 13 microM, respectively, and the type of inhibition by seenosides A and B with respect to allylamine as the substrate was non-competitive.

Anthraquinones↗

[Comparative study of the use of sennoside A and B vs polyethylene glycol and electrolytes in anterograde preparation of the colon].

OBJECTIVE: Compare effectiveness of antegrade bowel preparation by liquid diet, polyethylenglycol (PEG) and electrolytes solution plus sennosides A and B, vs. liquid diet plus sennosides A and B only. BACKGROUND DATA: Preparation for colonoscopy with a balanced solution (PEG and electrolytes) has some physiological advantages. Nonetheless, drawbacks of such preparation include nasty flavor, large volumes and low availability in our country. METHOD: A randomized, comparative, prospective, transversal and blind trial that included 200 patients scheduled for colonoscopy were randomly assigned (one hundred each group) to receive: group 1: liquid diet, sennosides A and B and a two litter of solution with PEG and electrolytes; and group 2: liquid diet plus sennosides A and B. Compliance, tolerance and effectiveness of both preparations were evaluated blindly. The results were assessed by Student's T test. RESULTS: The effectiveness of group 2 preparation proved superior (p < 0.05) to group 1. Tolerance and side effects were similar for both groups with no related complications.

Anthraquinones↗

[Transport and mode of action of sennosides].

Prior to attempting to develop a new laxative, pharmacodynamic studies were conducted on the individual active constituents of senna. Sennoside A, sennoside B and rhein were injected intravenously and were introduced into the isolated stomach, small bowel and large bowel of the anaesthetised pig. Blood, urine and bile, collected over 6 hours, were assayed by a novel fluorometric technique. Recoveries and measured oil water partition coefficients indicate that the sennosides are virtually non-absorbed in the stomach and small bowel. Following administrations outside the large bowel, anthracene derivative concentrations in the lumen and wall of the colon were below the limits of detection. Thus, a transport theory involving absorption and resecretion of sennosides into the large bowel is discounted. The results support a mode of action involving direct transport through the alimentary canal to the large bowel where micro-organism break the sugar-anthracene bonds. Derivatives of the liberated lipophilic aglycones are absorbed into the wall of the colon and stimulate the nerve plexuses thereby leading to defaecation. The "colon-specific" mode of action of the natural anthrone glycosides appears to be an ideal method of stimulating bowel action.

Animals↗

Bowel preparation for the total colonoscopy by 2,000 ml of balanced lavage solution (Golytely) and sennoside.

One of disadvantages of the Golytely preparation is that examinees have to drink as much as 4,000 ml of Golytely. To overcome this disadvantage, we designed a modified preparation regimen in which examinees have to drink only 2,000 ml of Golytely by taking sennoside orally. Bowel preparation was carried out in 297 examinees by this modified method. Examinees ate their usual diet and took 36 mg of sennoside orally on the night before the examination. On the day of the examination, the examinees drank a total of 2,000 ml of Golytely. No severe complications were noted and 97% of the examinees were able to drink the dose of 2,000 ml. Subjects who had also experienced bowel preparation by the modified method of Brown were asked to compare the two regimens, and only 1% preferred Brown's method while 73% preferred bowel preparation by our Golytely method. The result of bowel preparation by this method was excellent or good in 90 to 97% of the subjects at all sites in the colon and rectum. We conclude that bowel preparation for total colonoscopy using 2,000 ml of Golytely and sennoside is superior because it is highly acceptable to the examinees and provides excellent gut irrigation.

Adolescent↗