Effect Of Sennosides Research Articles

Sennoside-induced secretion is not caused by changes in mucosal permeability or Na+,K(+)-ATPase activity.

The effect of sennosides (50 mg kg-1) on the rat colon in-situ was studied 6 h after oral treatment when the laxative effect was maximal. In a second experiment, rhein (4 x 10(-3) M), an active sennoside metabolite, was administered into the lumen of the colon for 1 h. Both sennosides and rhein reduced net H2O and Na+ absorption or reversed it to net secretion. Paracellular permeability, as measured using erythritol as a small marker molecule, was increased 2- to 3-fold; permeability to a large molecule, PEG 1000, was unchanged. The activity of Na+,K(+)-ATPase in the colon mucosa was not affected. There was no damage of the epithelial cells as determined by lactic acid dehydrogenase release. These results indicate that neither inhibition of Na+,K(+)-ATPase nor damage of the colon epithelium are involved in the secretory effect of sennosides or rhein. The increased paracellular permeability of small molecules fits into the concept of stimulation of active chloride secretion by sennosides, which is electrochemically and osmotically balanced by an increase in Na+ and H2O flow via the paracellular pathway.

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.

大腸内視鏡検査の前処理としてのシサプリドとセンノシドの効果の比較検討

S状結腸までの観察を主目的とした大腸内視鏡検査 (S状結腸内視鏡検査) の前処置をより良好にすることを目的として, 緩下剤センノシド (s) と消化管運動賦活剤シサプリド (c) を検査前日に投与する方法の有用性を検討した.痔核等による肛門部症状があり大腸疾患スクリーニングのための大腸内視鏡検査を施行された99例の前処置を, 封筒法によって, (1) 当日GE120mlのみ施行する方法, (2) S (24mg分 1) を服用しGE120mlを施行する方法, (3) C (7.5mg分 3) を服用しGE120mlを施行する方法, (4) SとCの両方を服用しGE120mlを施行する方法の4法に分け, 内視鏡により初めて有形便がみえた部位, 大腸各部位の観察しやすさ, 挿入可能範囲などを検討した.その結果SとCの両方を前日服用し当日GEを施行する方法により, 直腸内の有形便が少量となり, 下行結腸が観察しやすくなり, 時に全大腸が観察できるなど, 本法は, 人間ドックなどで行われるS状結腸内視鏡検査の前処置法として有用と考えられた.

The effect of sennosides on colonic mucosal histology and quality and tolerance of bowel preparation

The effect of sennosides on colonic mucosal histology and quality and tolerance of bowel preparation

Effects of sennosides and nonanthranoid laxatives on cytochemistry of epithelial cells in rat colon.

The cytochemical effects of laxatives on rat colonic epithelial cells were studied. A total of 32 rats was divided into four groups. Three groups were treated with bisacodyl, picosulfate and sennosides for 12 weeks, and a fourth group served as control. The rectum, midcolon and cecum were studied for acidic mucins, lectin soybean agglutinin (SBA) and cytokeratin AE1. Most striking and consistent changes were found in the rectum including total acidic mucin content which significantly increased, with sulfomucin decreased and sialomucin increased in the three treatment groups. Cytokeratin AE1 expression increased on picosulfate and sennosides. SBA total binding increased on bisacodyl and picosulfate. The present findings were thought to be of functional origin and do not represent early precancerous lesions.

Effects of sennosides A + B and bisacodyl on rat large intestine.

Oral and intracecal administration of bisacodyl or sennosides A + B (10-100 mg/kg each) to rats induced a similar quantity of soft feces within 24 h and a similar acceleration of large intestinal transit time, but in each case bisacodyl had a prolonged action. Net fluid absorption in the perfused rat colon was reduced to a comparable extent by local bisacodyl in 1/10 of the molar concentration of rhein, an active metabolite of sennosides; recovery was delayed after bisacodyl. These results show that the time course of the laxative action of both drugs is different, probably attributable to their different pharmacokinetics. Both drugs influence colon motility as well as colonic secretion, but fluid secretion may contribute more to the laxative effect of bisacodyl than to that of sennosides.

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2.

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.

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.

Combined manometric and radiological study of the changes in colonic motility induced by sennosides in rats.

Colonic motility changes induced by sennosides in rats were studied by an original method, which permits the simultaneous projection of manometric and fluoroscopic registrations on a single monitor. The results of this study allowed us to confirm the laxative effect of sennosides by inducing mass movements within 60-80 min after intracecal administration leading to a complete emptying of the whole colon. These mass movements were preceded by hypotonia of cecum and colon and impeded pellet formation.