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PubMed1999

No clastogenic activity of a senna extract in the mouse micronucleus assay.

In previous studies, an analytically well-defined senna extract, commonly used as a laxative, gave positive responses in vitro in the Ames test and in the CHO assay. Therefore, the objective of this study was to investigate the genotoxic activity of the same senna extract in an in vivo genotoxicity assay by means of the generally acknowledged MNT. After administration of an oral dose of 2000 mg senna extract/kg to NMRI mice of both genders, which is equivalent to 119 mg potential rhein/kg, 5.74 mg potential aloeemodin/kg and 0. 28 mg potential emodin/kg, there were no elevated levels of micronuclei in bone marrow cells. Kinetic studies were performed in parallel to demonstrate target organ availability. Highest concentrations in the plasma were reached after 1 h with 3.4 microg rhein/ml and 0.065 microg aloeemodin/ml. In all cases, emodin was below the limit of quantification. From the results, the in vitro clastogenic activity of the senna extract could not be confirmed in the mouse micronucleus assay. Together with further negative in vivo genotoxicity studies with anthranoids, the conclusion can be drawn that there is no indication so far demonstrating a genotoxic risk for patients taking senna laxatives.

Animals↗
PubMed1996

Occupational asthma and rhinoconjunctivitis caused by senna.

Occupational sensitization to senna is seldom reported. We describe a 21-year-old male atopic factory worker who developed IgE-mediated asthma and rhinoconjunctivitis 5 months after exposure to senna while he was working for a company manufacturing hair dyes. In the bronchial challenge test with senna, he exhibited a strong reaction. The skin prick test gave a 12-mm wheal reaction. The radioallergosorbent test (RAST) with senna was highly positive (33.6 PRU/ml, class 4), and could not be inhibited with pollens or foods. In protein staining with SDS-PAGE, two heavy bands were detected in senna at about 14 and 25 kDa, and two faint bands were visible at 19 and 21 kDa, In IgE immunoblotting with the patient's serum, one heavy band was detected at about 16 and four faint bands at 23, 25, 28, and 38 kDa. The patient became symptom free after he had changed his job within the same company.

Adult↗
PubMed1985

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↗
PubMed1993

Effect of senna is not mediated by platelet-activating factor.

The effect of in vivo treatment with senna was examined on the ex vivo formation of platelet-activating factor (PAF) by small and large intestine of rat, mouse and guinea pig. A single or a prolonged oral administration of senna (60-240 mg/kg) to animals did not increase intestinal PAF content. Nor did senna increase the intraluminal release of acid phosphatase. A similar result was obtained in the colonic tissue of rat perfused in vitro with rhein (1-500 micrograms/ml) or rhein anthrone (1-500 micrograms/ml). In contrast, a single oral administration of phenolphthalein (20 mg/kg), bile salts (20 mg/kg) or magnesium sulfate (30 mg/kg) to rats increased intestinal PAF content. Magnesium sulfate also increased the intraluminal release of acid phosphatase. Colonic tissue of rats perfused in vitro with calcium ionophore A23187 (10 micrograms/ml) formed large amounts of PAF and acid phosphatase. PAF stimulates intestinal motility and secretion and mediates gut damage while acid phosphatase is a marker of cellular damage. Therefore, our data suggest that senna is well tolerated in animals and PAF does not mediate senna-induced laxation.

Acid Phosphatase↗
PubMed2003

Skin breakdown and blisters from senna-containing laxatives in young children.

BACKGROUND: At the direction of the Food and Drug Administration, phenolphthalein was removed from all over-the-counter laxatives in 1999. Phenolphthalein was then replaced in most laxative products with the natural product senna from Cassia acutifolia Delile, which contains various anthraquinones. No data are available on the safety of senna use in children <6 years of age. OBJECTIVE: To describe the clinical outcomes of exposure to unintentional ingestion of senna-containing laxatives in young children. METHODS: All ingestion exposures of senna-containing laxatives in children <5 years of age from 6 poison centers over a 9-month period were evaluated. Inclusion criteria required 24-hour follow-up and the presence of diarrhea to confirm ingestion. Parents were told routinely that severe diaper rash was possible and to protect the perianal area with frequent cleansing and a barrier ointment if the child was wearing diapers. RESULTS: During the study period, 111 cases were reported: 19 children experienced no diarrhea, 4 were lost to follow-up, and 88 exposures were evaluated. Fifty-two children (59%) were </=2 years old. Fifty children remained in diapers, 28 children were fully toilet trained, and 10 wore diapers (pull-up pants) overnight. Twenty-nine children (33%) experienced severe diaper rash. The mean +/- SD time to recognition of the diaper rash was 15.6 +/- 8.6 hours. Ten children (11%) had blisters and skin sloughing. There was a significant increase in severe diaper rash (p < 0.05) and onset of blisters and skin breakdown (p < 0.05) in children wearing diapers versus those who were fully toilet trained. The mean time to onset of blisters was 14.5 +/- 6.8 hours. Skin burns and loss were seen primarily on the buttocks and perineum, loosely following the diaper area. CONCLUSIONS: Unintentional ingestion of senna-containing laxatives in young children may potentially cause severe diaper rash, blisters, and skin sloughing.

Blister↗
PubMed1987

Comparative laxation of psyllium with and without senna in an ambulatory constipated population.

Our short-term study used objective and subjective criteria to evaluate the ability of two laxative preparations to relieve constipation. Forty-two adults who were constipated, i.e., had less than or equal to 3 bowel movements during 1 wk of a single-blind placebo treatment, were randomized to receive psyllium (7.2 g/day) or psyllium plus senna (6.5 + 1.5 g/day). Both laxatives increased defecation frequency and wet and dry stool weights although the added effect of the senna was clearly evident. Only the psyllium with senna increased stool moisture. Two distinct responses to the psyllium plus senna were evident; the subpopulation of high responders (n = 7) was responsible for most of the increase in stool frequency and dry weight in this group, and laxation in the subpopulation of normal responders (n = 12) was similar to that observed in those receiving psyllium alone. Both laxatives provided a similarly high degree of subjective relief and improvement in stool consistency. When constipation was assessed objectively by stool frequency and weight, laxation was attained by 63% of the psyllium plus senna group and 48% of the psyllium group.

Adult↗
PubMed1996

Selective uptake of intraluminal dextran sulfate sodium and senna by macrophages in the cecal mucosa of the guinea pig.

The involvement of macrophages in the passage of intraluminal substances into the lamina propria was examined in the large intestine of the guinea pig. Dextran sulfate sodium (DSS) and senna, which, experimentally, induce ulcerative colitis and melanosis coli, respectively, were chosen for examination, since these substances are visible under the microscope without any special treatment. DSS (MW 50,000) and senna were orally administered to guinea pigs. In tissue sections of the intestine, the presence of DSS was demonstrated by toluidine blue staining, while senna was visible under the light microscope as brown pigment. In the large intestine of guinea pigs, macrophages were most numerous in the cecum, decreasing in number towards the rectum. Metachromatic reaction due to DSS was first recognized in the epithelium of the cecum, and was subsequently incorporated by macrophages. The presence of DSS, either in the epithelium or in macrophages, was not recognized in the small intestine or the distal colon. Senna pigmentation was also limited to the cecum and proximal colon, in which pigmented macrophages aggregated in the lamina propria. The two different substances administered orally were taken up in the cecum, and partly also in the proximal colon; the substances passed through the epithelium and were incorporated by macrophages. This finding suggests the existence of a weak point in the intestinal barrier in this particular portion of the intestine.

Animals↗
PubMed1994

Comparative effects of intraduodenal psyllium and senna on canine small bowel motility.

BACKGROUND/AIM: To define the possible contribution of altered small intestinal motor activity to side-effects of bulking fibres, we sought to compare the relative effects of intraduodenal and intracolonic administration of the bulking fibre psyllium and the anthraquinone laxative senna on canine small intestinal motor activity. METHODS: Motor activity was recorded by serosal strain gauges implanted along the small intestine in 6 dogs. In random order, the motor responses to the instillation of psyllium (in doses of 5 or 10 g), senna (10 mg/kg) or appropriate vehicle (200 ml water infusion or saline 5 ml bolus) into either the proximal duodenum or proximal colon were assessed. RESULTS: The intra-duodenal administration of psyllium in either dose consistently induced a prolonged burst of 'clustered' contractions; in contrast, clusters were infrequent and of short duration following instillation of either vehicle or senna (P < 0.05). Intraduodenal instillation of psyllium inhibited migrating motor complex (MMC) migration and consistently delayed the onset of the next MMC cycle; a similar inhibition occurred with vehicle, however. Neither senna nor its vehicle inhibited MMC migration. None of these agents had any effect on small intestinal motor activity when instilled directly into the colon. CONCLUSIONS: Psyllium administered directly into the duodenum inhibits MMC activity and consistently induces 'clustered' contractions. Whilst the MMC-inhibitory effect appears to be a non-specific volume-related phenomenon, the induction of clusters is independent of volume or laxation. These motor effects of psyllium may contribute to the gastrointestinal symptomatology related to such agents and could be avoided by the preferential release of psyllium in the colon.

Animals↗
PubMed1991

Asthma and allergy associated with occupational exposure to ispaghula and senna products in a pharmaceutical work force.

A cross-sectional study of 125 pharmaceutical workers engaged in the manufacture of bulk laxatives based on ispaghula husks (psyllium) and senna pods was conducted. Skin prick tests with extracts of these components revealed that 7.6% were allergic to ispaghula and 15.3% were allergic to senna. Four (3.2%) cases of occupational asthma were identified. The overall prevalence of asthma (6.4%) was less than in a comparable nonexposed Australian population (odds ration, 0.44). Symptoms referrable to the upper airways, eyes, and skin were more prevalent (52.0%) than in the reference population (odds ratio, 1.53). Smokers and nonatopic subjects were more likely to complain of these symptoms if they were sensitized to senna and/or ispaghula than if they were not sensitized (relative risks, 1.9 and 2.6, respectively). Sensitization to ispaghula and/or senna was not a risk factor for asthma. An IgE-mediated allergic mechanism is probably responsible for the allergic symptoms in many of these subjects. Smoking seems to be a cofactor in this process.

Asthma↗
PubMed2005

Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides.

OBJECTIVE: To report a case of chronic ingestion of very large amounts of senna fruits as an herbal tea, possibly leading to severe hepatotoxicity. CASE SUMMARY: A 52-year-old woman who had ingested, for >3 years, one liter of an herbal tea each day made from a bag containing 70 g of dry senna fruits, developed acute hepatic failure and renal impairment requiring intensive care therapy. The severity of the hepatic failure was reflected by the increase in prothrombin time (international normalized ratio >7) and the development of encephalopathy. Liver transplantation was discussed, but the patient ultimately recovered with supportive therapy. Renal impairment was consistent with proximal tubular acidosis, also with marked polyuria refractory to vasopressin administration. Suprisingly, large amounts of cadmium were transiently recovered in the urine. DISCUSSION: Cassia acutifolia and angustifolia plants are widely used as laxatives. Their chronic abuse may be associated with serious manifestations, including fluid and electrolyte loss, with chronic diarrhea. Severe hepatotoxicity is unusual, but could be explained by the exposure of the liver to unusual amounts of toxic metabolites of anthraquinone glycosides (sennosides). An objective causality assessment suggests that hepatotoxicity was possibly related to senna laxative abuse. Regarding nephrotoxicity, there are no available human data on sennosides, while experimental models suggest that anthraquinone derivatives may also accumulate in the kidneys. The finding of high urinary concentrations of cadmium would suggest contamination of the herbal tea by metals, but this hypothesis could not be verified. CONCLUSIONS: Ingestion of large doses of senna laxatives may expose people to the risk of hepatotoxicity.

Acidosis↗
PubMed2001

A mosaic disease of Senna hirsuta induced by a potyvirus in Nigeria.

A virus inducing mosaic and severe leaf malformation, isolated from Senna hirsuta in Nigeria, was studied. The virus had a rather narrow host range, infecting a few species in Caesalpinaceae, Chenopodiaceae and Fabaceae families. The virus was widespread in southern Nigeria with prevalence ranging from 74% to 86.4% in some locations. It was transmitted mechanically and in a non-persistent manner by Myzuspersicae, Aphis craccivora and A. spiraecola. There was no evidence of transmission by seeds. Electron microscopy of leaf dip preparations revealed flexuous rod-shaped particles. The viral coat protein had Mr of 32.5 K. The virus reacted positively with a monoclonal antibody (MAb) to peanut stripe virus specific for potyviruses (members of the Potvvirus genus) and with antisera to turnip mosaic virus (TuMV), potato virus Y (PVY), TuMV, potato virus A (PVA), potato virus V (PVV) and bean yellow mosaic virus (BYMV), but it failed to react with antisera to celery mosaic virrus (CeMV), bean common mosaic virus (BCMV), soybean mosaic virus (SMV), and clover yellow mosaic virus (ClYMV) in plate-trapped ELISA (PTA-ELISA). No positive reaction was obtained when the virus was tested against any of the antisera in double-antibody sandwich ELISA (DAS-ELISA). This is the first report of natural infection of Senna species in Nigeria. The virus, tentatively designated as Senna mosaic virus (SeMV), seems to differ from other viruses previously described from Senna species in the literature and indeed other legume potyviruses in Nigeria.

Capsid↗
PubMed1997

Assessment of the genotoxic risk from laxative senna products.

Laxative senna products and several of their specific components have been submitted to a large number of genetic tests. While most studies gave negative responses, results from some of the studies suggest that components of senna products, particularly emodin and aloe-emodin, have genotoxic activity. Assessment of the genotoxicity profile of these substances, in light of other data from animal and human metabolism or kinetic studies, human clinical trials and rodent carcinogenicity studies do not support concerns that senna laxatives pose a genotoxic risk to humans when consumed under prescribed use conditions.

Aloe↗
PubMed2004

A 13-week oral toxicity study of senna in the rat with an 8-week recovery period.

Senna was administered by gavage to Sprague Dawley rats once daily at dose levels of 0, 100, 300, 750 or 1500 mg/kg for up to 13 consecutive weeks followed by an 8-week recovery period for selected animals. Dose- and treatment-related clinical signs included abnormal feces, which were seen to varying degrees from animals at 300 mg/kg per day and more. Animals receiving 750 or 1500 mg/kg per day had significantly reduced body weight gain (males only) and, related to the laxative properties of senna, increased water consumption and notable changes in electrolytes in both serum and urine. At both the terminal and recovery phase necropsy, an increase in absolute and relative kidney weights was seen for male and female animals receiving 750 and/or 1500 mg/kg per day. A dark discoloration of the kidneys was observed at necropsy along with histopathological changes in the kidneys (slight to moderate tubular basophilia and pigment deposits) at 300 mg/kg and above. However, there were no indications in laboratory parameters of any renal dysfunction. In addition, for all treated groups, minimal to slight hyperplasia was recorded in the forestomach and large intestine. Following 8 weeks of recovery, with the exception of the brown pigment in the kidneys, there were no histopathological abnormalities. Thus, the biochemical and morphological changes seen following 13 weeks of treatment of senna significantly reversed following 8 weeks of recovery.

Administration, Oral↗
PubMed1996

NG-nitro-L-arginine methyl ester reduces senna- and cascara-induced diarrhoea and fluid secretion in the rat.

Senna (60 mg/kg orally) and cascara (800 mg/kg orally)-induced diarrhoea and net fluid secretion were studied in rats for a time period of 1-8 h. NG-Nitro-L-arginine methyl ester (L-NAME) (2.5-25 mg/kg i.p. twice, 15 min before and 4 h after laxative administration), an inhibitor of nitric oxide synthase, reduced the diarrhoeal response. This effect was counteracted by L-arginine (600 and 1500 mg/kg i.p. 15 min before laxative administration), the precursor of nitric oxide (NO). The senna- and cascara-stimulated fluid secretion was reduced by NG-nitro-L-arginine methyl ester 25 mg/kg i.p. (twice, 15 min before and 4 h after laxative administration), while the stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) 25 mg/kg i.p. was without effect. These results suggest a possible involvement of NO in senna- and cascara-induced diarrhoea and fluid secretion.

Animals↗
PubMed1998

Efficacy of senna versus lactulose in terminal cancer patients treated with opioids.

The best laxative for terminal cancer patients treated with opioids still remains to be determined. This comparative study was conducted with the objective of determining treatment and cost efficiency for senna and lactulose in terminal cancer patients treated with opioids. The methodology used a randomized, open, parallel group design. The study was conducted in the Palliative Care Unit in one Madrid Health Care District. Ninety-one terminal cancer patients were randomized into two groups: A = treated with senna (starting with 0.4 mL daily), and B = treated with lactulose (starting with 15 mL daily) for a 27-day period. The main outcome measures were defecation-free intervals of 72 hr, days with defecation, general health status, and treatment cost. Laxative efficacy was analyzed through t test and analysis of variance. No difference was found between the laxatives in defecation-free intervals or in days with defecation. The final scores for general health status were similar in both groups. Given that the two treatments have similar efficacy and adverse effects, a recommendation is made for the use of senna because its cost is lower than lactulose.

Adult↗
PubMed2003

Effects of long-term administration of Senna occidentalis seeds in the large bowel of rats.

Plants of the genus Senna that contain anthranoides derivatives are frequently used as cathartics. Radiological studies have demonstrated that patients with chronic constipation who have used stimulant laxative have colonic redundancy and dilatation more frequently than patients who have not. The objective of the present work was to study morphological and histochemical changes of the lower gut after administration of Senna occidentalis seeds for a long period to rats, as observed in skeletal muscle fibers. Fragments of the lower gut of young and adult rats treated with S. occidentalis seeds (2% for 171 days and 3% for 61 days in the diet) were submitted to histological and histochemical analysis and to densitometry. The most important finding was decreased oxidative enzyme activity in smooth muscle cells and in myenteric neurons of the large bowel. As oxidative metabolism is essential for ATP and energy production, these results suggest that the functional intestinal disturbance caused by the chronic use of Senna occidentalis as a laxative can be due to a metabolic effect involving energy production, which would decrease colonic motility and cause functional colonic dilatation, but without any irreversible anatomic change.

Animals↗
PubMed2000

Influence of a highly purified senna extract on colonic epithelium.

BACKGROUND: Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls. AIMS: To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression. METHODS: Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically. RESULTS: Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased. CONCLUSION: Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.

Adolescent↗
PubMed1988

Senna--an old drug in modern research.

Senna was introduced in therapy in the 9th century by the Arabs. In the second half of the 19th century chemical investigation of the drug was undertaken, but only a century later the sennosides were isolated. Pharmacological research on senna started at the beginning of this century. During the last 25 years interest in the pharmacology of synthetic and natural laxatives steadily increased. Senna, containing only dianthrones as active substances, is still in the center of scientific research and merits this special attention.

Arabia↗