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Laxative potency and acute toxicity of some anthraquinone derivatives, senna extracts and fractions of senna extracts.

This paper investigates the laxative effect and acute toxicity of certain fractions of senna extracts in mice. The same tests were also carried out with several pure anthraquinone derivatives common in senna pods. The results show that the laxative and toxic components of senna pods and senna extracts can be separated. The most potent laxative components, sennosides A + B and Fraction V (relative potencies 1 and 0.9 respectively), have the lowest toxicity (relative intravenous toxicities 1 and less than 1). Fractions with very low laxative activity (rhein-8-glucoside and Fraction IV, relative potencies 0.56 and 0.05) have the highest acute toxicity (relative toxicities 10 and 32 respectively).

Animals

Evaluation of the usefulness of dimethicone and/or senna extract in improving the visualization of abdominal organs.

Intestinal gas is the most common cause of technically unsatisfactory abdominal ultrasound scans. In the attempt to increase the visualization of abdominal organs, many investigators use antifoaming agents or laxatives. In the present, randomized, placebo-controlled, double-blind trial, a liquid dimethicone preparation and an extract of senna, alone and in combination, were tested as a means to improve scan quality. Response variables were defined on the basis of pancreas, aorta, and kidney visibility. There was no difference in the response variables of the three groups compared to placebo (P greater than 0.3-0.55). The results suggest that neither dimethicone nor senna improves the visibility of abdominal organs in ultrasound examination.

Abdomen

Mutagenicity of crude senna and senna glycosides in Salmonella typhimurium.

The mutagenicity of senna glycosides and extracts of senna folium and senna fructus was investigated in the Salmonella typhimurium reversion assay. Senna glycosides were inactive in all strains, except for a slight, but significant increase in mutant frequency in TA102 in the absence and presence of liver microsomes. Extracts of senna fructus and senna folium demonstrated weak activity in TA97a, TA100 and TA102 in the presence of liver microsomes, and in TA97a and TA102 in the absence of liver microsomes. A strong increase in mutant frequency (3- to 5-fold above background frequency) was observed with all extracts in TA98 in the presence of liver microsomes. This activity increased further following enzymatic hydrolysis with hesperidinase of extracts of senna fructus from one source, and could be correlated to the release of the flavonol aglycones kaempferol and quercetin. The weak or lacking activity of anthraquinone aglycones in the tested strains of Salmonella typhimurium indicates that mutagenicity can not be attributed solely to the anthraquinone content of these plant materials. The chemical nature of other mutagenic components has not been elucidated.

Animals

Reproducibility studies and effects of bowel preparations on measurements of rectal epithelial proliferation.

Measurements of rectal epithelial proliferation (REP), using tritiated labelled thymidine, correlate with colonic epithelial proliferation, risk for cancer and response to therapies. There have been criticisms regarding its reproducibility and the possible deleterious effects of bowel preparations on this biomarker. We studied paired observations on 7 patients repeated without bowel preparation, 11 repeated after tap-water enema, and 8 repeated after PEG-electrolyte solution or extract of senna purgative and found no significant differences between paired observations. In addition, in a high-risk group for colorectal cancer, 31 persons received PEG or senna preparation and their REP was not significantly different from that of 23 examined without these preparations. Thus, REP is a reproducible biomarker and not affected by several commonly used bowel preparations.

Biopsy

Stimulation of PGE2 synthesis and water and electrolyte secretion by senna anthraquinones is inhibited by indomethacin.

The effect of dried senna pod extract, containing 10% sennoside B, on colonic electrolyte and fluid transport was examined in the anaesthetized rat in-situ. Oral administration of senna pod extract dose-dependently (17.5-30 mg kg-1, calculated as sennoside B) reversed net absorption of water, sodium and chloride to net secretion and increased potassium secretion. Senna pod extract stimulated the output of prostaglandin E2 into the colonic lumen. Inhibition of prostaglandin biosynthesis by pretreatment of the rats with indomethacin (10 mg kg-1) significantly inhibited the effects of senna pod extract (17.5-30 mg kg-1) both on net fluid transport and on prostaglandin E2 synthesis. The inhibitory effect of indomethacin on net fluid transport induced by senna pod extract (30 mg kg-1) was dose-dependent. It is concluded that anthraquinones exert their laxative action at least partially via stimulation of colonic fluid and electrolyte secretion, and that this secretion is mediated by stimulation of endogenous prostaglandin E2 formation.

Animals

Prostaglandin-mediated action of sennosides.

The aim of this study was to investigate whether prostaglandins (PG) are involved in the mediation of sennoside-induced colonic fluid and electrolyte secretion. Oral administration of senna pod extract dose-dependently reversed net absorption of water, sodium and chloride to net secretion, increased potassium secretion and stimulated the release of PGE2 into the colonic lumen. Inhibition of PG biosynthesis by pretreatment of the rats with indomethacin significantly inhibited the effects of senna pod extract both on net fluid transport and on PGE2 release. The inhibitory effect of indomethacin on net fluid transport induced by senna pod extract was dose-dependent. It is concluded that sennosides exert their laxative action at least partially via stimulation of colonic fluid and electrolyte secretion, and that this secretion is mediated by stimulation of endogenous PGE2 formation.

Animals

Senna still causes laxation in rats maintained on a diet deficient in essential fatty acids.

The laxative effect of senna has been investigated in normal and essential fatty acid deficient (EFAD) rats. Oral administration of senna pod extract (7-5-90 mg kg-1) produced a dose-dependent increase in the number of soft faeces excreted by normal rats. Senna 30 mg kg-1 also reversed net absorption of water and increased the prostaglandin (PG) production in the colonic lumen of normal rats by about four times. Oral administration of senna pod extract to rats, maintained on a fat-free diet for 30-90 days, produced diarrhoea and reversed net absorption of water as in normal rats. However, a fat-free diet reduced the PG production drastically in the colonic lumen both in senna-free rats and in senna-treated rats. In EFAD rats carrageenan oedema, but not dextran oedema, was also drastically reduced. Since PG mediation is not present in EFAD rats we conclude that the PG are not essential for laxation induced by senna and that water secretion and PG production in the rat intestinal lumen are unrelated.

Animals

Pseudohyperaldosteronism from liquorice-containing laxatives.

Four cases of pseudohyperaldosteronism due to chronic ingestion of liquorice-containing laxatives are described. All patients had hypertension and hypokalemia with suppression of plasma renin activity and aldosterone; the diagnosis was based only on retrospective grounds. In patients with hypokalemia and hypertension a possibility of such a cause must be excluded to avoid unnecessary diagnostic procedures.

Adult

Rapid and simple determination of sennoside A and B in rhei rhizoma by ion-pair high-performance liquid chromatography.

A simple and precise ion-pair high-performance liquid chromatographic method was developed for the determination of sennoside A and B in Rhei Rhizoma. A reversed-phase chromatographic system consisting of a chemically bonded ODS silica gel column with an acetate buffer (pH 5.0)-acetonitrile (68:32), containing 5 mM tetra-n-heptylammonium bromide, as the mobile phase was used. Sennoside A and B in this crude drug were separated and determined within 20 min after direct injection of the solution extracted with 70% methanol. The results for various samples are presented.

Anthraquinones