Alexandrian Senna (Senna alexandrina Mill.)
1. Identity: Botanical Classification, Names, and Forms
Accepted Botanical Name and Synonyms
The currently accepted botanical name for Alexandrian senna is Senna alexandrina P. Mill., with major synonyms including Cassia senna L. and Cassia acutifolia Del. The closely related Indian or Tinnevelly senna is Cassia angustifolia Vahl. Senna alexandrina Mill. was recently acknowledged as the correct unified name for what was previously classified as two separate species. The plant belongs to the family Leguminosae (Caesalpinioideae). Additional synonyms include Cassia lanceolata Forssk.
Senna leaves consist of the dried leaflets of Cassia senna L. (Cassia acutifolia Delile), known as Alexandrian or Khartoum senna, or Cassia angustifolia Vahl, known as Tinnevelly senna, or a mixture of the two species. In commerce, both botanical sources are widely treated as equivalent, sharing similar chemistry and pharmacology, and both appear in official pharmacopoeias.
Common Names and Nomenclature
Alexandrian senna is also known as Egyptian senna, Tinnevelly senna (C. angustifolia Vahl), East Indian senna, or the French séné de la palthe. It received the names Alexandrian senna and Egyptian senna because Alexandria in Egypt was the main trade port in past times. In Arabic, it is called Sanna Mekki (سنا مكى) or Salamekki (سالمكى).
Plant Description and Geographic Origin
The plant is a shrub usually 0.7 to 1 m tall, native to Africa, India, and Asia, and cultivated in Sudan, China, India, and Pakistan. The plants have compound pinnate leaves with three to eight pairs of leaflets per leaf. Lanceolate and pale-green leaflets are 1.5 to 5 cm long and 5 to 15 mm wide. Commercial senna comes from Egypt, Sudan, and India. S. alexandrina has a long tradition of use and has been an important item of trade, especially in Arabic medicine. Senna is now a pan-tropical species but mostly grown in Southern India for commerce.
Parts Used and Preparations
The parts used medicinally are the pods, stems, and leaves. In the United States, senna is available as a tablet (sennosides), fluid extract, leaf, pod, oral solution, or tea. Senna products are used for the short-term relief of occasional constipation and are available both on prescription and over-the-counter. Dried senna pods, and the leaves — often as tea bags — are sometimes used to make an infusion (tea). Commercially, senna preparations are available as sennosides, standardized senna concentrate, and standardized senna fruit extract; dosage is conventionally expressed in terms of sennosides.
Regulatory Status
The FDA lists Alexandrian senna (Cassia acutifolia Delile) as a natural flavoring substance for use in food (21 CFR § 172.510). It is approved in the US as a laxative for short-term treatment of constipation and is an FDA-approved over-the-counter (OTC) laxative. It is on the World Health Organization's List of Essential Medicines. In 2023, it was the 302nd most commonly prescribed medication in the United States, with more than 300,000 prescriptions.
2. Traditional and Historical Use
Origins in Arab and Islamic Medicine
Senna was first used medicinally by Arabian physicians in the 9th century AD. The plant's name is derived from the Arabic word sena and the Hebrew word cassia, which means "peeled back," a reference to its peelable bark. It was introduced into European medicine by the Arabs in the 9th or 10th century, and its laxative properties were already known at that time.
Out of 250–300 accepted species of Senna distributed throughout the world, Cassia angustifolia (Senna Makki) and Cassia acutifolia (Alexandrian senna) are officially mentioned in various pharmacopoeias. Historically, medicinal use dates back to the 9th–10th centuries, with Arabian physicians employing its leaves and pods for different ailments.
The Arabs used senna among a range of important medicinal plants. Sennae folium was employed as a mild laxative, replacing harsher purgatives such as Helleborus odorus and Euphorbium that had been used until then.
Spread into European and Western Medicine
Senna has long been used in traditional Arabian and European medicine, primarily as a cathartic. The leaves were brewed into a tea and administered as a strong laxative. Because it is often difficult to control the concentration of active ingredients in the tea, its effects may be unpredictable.
The Austrian Pharmacopoeia of 1812 lists senna leaves as "infusum laxativum." In the "American Materia Medica, Therapeutics and Pharmacognosy" of Finley Ellingwood (1919), "Alexandria Senna" is described as an efficient remedy, mild, kindly, certain and uniform in its action.
Ayurvedic and Indian Traditions
Senna is a 1–2 m high, undershrub legume plant. In the Indian subcontinent, it has been cultivated and used in traditional medicine in parallel with its Arabic lineage. The leaves and fruits of the senna plant were used to an equal extent.
Traditional Preparation and Indications
Extracts of the leaves, flowers and fruit of senna have been used for centuries in folk medicine as a laxative and stimulant. Senna is also included in several herbal teas, used for purging and in weight loss. Traditional properties attributed to the plant include bitter, digestive, laxative, and antimicrobial actions, with traditional indications including constipation, inflammatory skin conditions, hypertension, and obesity. As a laxative, 1–2 g of the powder was traditionally mixed with jaggery and given orally.
3. Key Constituents and Active Compounds
Primary Active Compounds: Sennosides
The active components in senna extracts are anthraquinone derivatives and their glucosides, referred to as senna glycosides or sennosides. Sennosides A and B (approximately 2.5%), which are rhein-dianthrone di-glycosidic aminoanthraquinones, are the principal active ingredients. Dianthrone O-glycosides are major proactive constituents and make up 1.3% to 3.9% (w/w) of senna pods or leaves. Sennosides A and B are stereoisomers.
The active constituents are the anthranoids present in the leaf as dianthrones (75–80%) and as anthrones (20–25%). The amount of anthranoids of the emodin and aloe-emodin type is generally higher in the leaves than in the fruits.
The herbal substance contains not less than 2.5 percent of hydroxyanthracene glycosides, calculated as sennoside B (C₄₂H₃₈O₂₀; Mr 863).
Other Phytochemical Constituents
Additional chemical constituents include anthraquinone glycosides (sennosides, aloe-emodin, rhein), beta-sitosterol, flavones, tartaric acid, mucin, essential oil, mucilage, tannin, and resin. The senna plant contains a multitude of chemical components including dianthrones, anthraquinones, naphthalene derivatives, and flavonoids. Other dianthrone diglycosides, aminoanthraquinone glycosides, and aglycones are found in trace amounts in herbal preparations.
Distinguishing Alexandrian from Indian Senna
Both species can be distinguished from each other chemically: tinnevellin glucoside is found only in Cassia angustifolia (Indian senna) and is absent in C. senna (Alexandrian senna).
4. Established Mechanisms of Action
Prodrug Activation by Colonic Bacteria
Sennosides are prodrugs that are not absorbed by the gastrointestinal tract. They are hydrolyzed by enteric bacteria into active rheinanthrone monoanthrones, which increase colonic motility. Sennosides, the most popular stimulant laxatives, can be transformed to an active metabolite, rhein anthrone, which leads to purgative action in the intestine.
Dual Mechanisms of Laxative Action
Rhein-anthrone-induced laxative effects occur through two distinct mechanisms: an increase in intestinal fluid transport, which causes accumulation of fluid intraluminally, and an increase in intestinal motility.
The gut bacteria convert sennosides into rheinanthrone and rhein, the active metabolites responsible for the laxative effect. Over 90% of sennosides and their metabolites are excreted in the feces. The secretory action involves stimulation of prostaglandin E2 production, which increases chloride ion secretion and attendant changes in luminal water content. The motor action involves rheinanthrone and rhein directly stimulating colonic peristalsis, accelerating transit time.
More recent evidence shows that stimulant laxatives alter fluid and electrolyte absorption, producing net intestinal fluid accumulation and laxation. Senna increases concentrations of cyclic 3',5'-adenosine monophosphate (cAMP) in colonic mucosal cells and may alter the permeability of these cells and mediate active ion secretion, producing net fluid accumulation and laxative action.
An interaction between rhein anthrone, the active metabolite of the sennosides, and the immune cells of the colon has been suggested as a basis for laxative activity.
Selectivity of Effect
Senna mainly promotes evacuation of the colon, with limited action on more proximal segments of the gastrointestinal tract. It displays the most gentle purgative action of the stimulant laxatives.
5. Scientific Evidence by Area of Use
5.1 Occasional and Chronic Constipation
The efficacy of senna preparations has been evaluated in clinical trials in the treatment of constipation and for bowel cleansing before radiological investigations or colonoscopy. In the majority of the studies, combinations of senna with fiber were investigated.
Senna leaves preparations have to be regarded as herbal medicinal products with a "well-established medicinal use" in the indication of short-term treatment of occasional constipation with respect to the EU Directive on medicinal products.
A small study in middle-aged adults with chronic idiopathic constipation showed that 500 mg of senna taken twice daily for 4 weeks was as effective as 500 mg of magnesium oxide taken three times daily. Clinical trials evaluated senna for only 4 weeks. Longer-term use is probably appropriate for chronic constipation management, though data on long-term tolerance and side effects are limited. No evidence of tolerance development has been found in available studies.
According to the CPMP core-SPC, senna leaves are intended "for short-term use in cases of occasional constipation." The EMA and ESCOP recommend short-term use of senna to treat occasional constipation. The overall evidence base for senna in occasional constipation is considered strong, supported by decades of clinical use, pharmacological data, and well-established regulatory recognition, although the body of large-scale randomized controlled trial data specifically for senna alone is more limited than for some comparator laxatives.
5.2 Opioid-Induced Constipation
Once any impactions have been eliminated, a regular regimen of senna and docusate is commonly recommended for opioid-induced constipation management. First-choice laxatives in opioid-induced constipation include bisacodyl, sodium picosulfate, senna, and macrogol, according to clinical guideline algorithms.
A retrospective cohort study compared patients who received senna matched with similar patients who received other oral bowel medications, to determine the subsequent risk of "problematic constipation," in hospitalized pediatric oncology patients less than 21 years of age, across 78 children's and adult hospitals between 2006 and 2011 who were started on seven or more consecutive days of opioid therapy. After performing propensity score matching, Cox regression modeling was used to compare the subsequent hazard, and the conclusion was that initiating senna therapy, compared with other oral bowel medications, diminishes the subsequent risk of surrogate markers of problematic constipation in this population.
In a crossover randomized trial, outpatients aged 18 or older with cancer at risk of or experiencing opioid-induced constipation were randomly assigned to begin a standard bowel protocol of escalating doses of sennosides or polyethylene glycol (PEG), plus a dummy preparation. After 3 weeks, patients switched to the alternate active product. Constipation was assessed using the revised Victoria Bowel Performance Scale (rBPS) for the number of days with a satisfactory bowel movement, the time in days to goal rBPS, and treatment preference. Seventy patients were recruited, with 42 completing their first treatment period and 28 completing both treatment periods. For the typical patient, the expected number of days with a satisfactory bowel movement per days of treatment was found to be 1.21 times higher on PEG than on sennosides (95% credible interval 0.96 to 1.55), a result that was not conclusively superior for either agent and was limited by high dropout.
The evidence supporting senna in opioid-induced constipation is moderate: senna is widely recommended in clinical guidelines as a first-line agent, but comparative superiority over other laxatives in this indication has not been definitively established in large randomized controlled trials.
5.3 Bowel Preparation Before Colonoscopy
Senna is used orally to empty the bowel prior to surgery or radiologic, proctoscopic, or endoscopic procedures. Senna has also been used in a very high dosage form to clear the colon before radiological examination.
Frigerio et al. (1996) compared doses of senna (X-Prep®, a senna fruit dry extract preparation corresponding to 150 mg hydroxyanthracene glycosides, calculated as sennoside B, per single dose) for colon cleansing. 473 patients (225 males and 248 females, mean age 59.7 years, range 14–96 years) referred for colonoscopy participated in the randomised, single-blind study. 250 patients received a dose of the solution equivalent to 150 mg sennosides in a single administration the evening before the examination.
In a prospective randomized investigator-blinded clinical trial, patients assigned to the senna group were instructed to take 24 tablets in divided doses — the first twelve at 2 P.M. and the other twelve at 10 P.M. — the day before colonoscopy, and were advised to drink clear liquids. Each senna tablet contained 9–11 mg of Sennoside A and B. The investigators concluded that senna has the same efficacy and patient acceptance as polyethylene glycol-electrolyte solution (PEG-ES), and that it could be prescribed as an alternative method for bowel preparation.
In a randomized controlled study on 474 patients, bowel cleansing was found to be better with sennoside A+B compared to PEG, but abdominal pain was more common in the senna group. Another randomized controlled study on 322 patients found no difference in effectiveness between the two agents.
The evidence for senna as a bowel preparation agent is moderate to good based on multiple randomized clinical trials, where it has performed comparably to PEG-electrolyte solutions in terms of colonic cleansing quality, though with a higher rate of abdominal cramping in some studies.
5.4 Other Investigated Areas (Evidence Weak or Absent)
People also use senna for irritable bowel syndrome (IBS), hemorrhoids, weight loss, and many other conditions, but there is no good scientific evidence to support these uses. These uses have not been validated in adequately powered clinical trials, and no regulatory authority has approved senna for these indications.
Accumulating pre-clinical evidence suggests that sennoside A possesses pharmacological properties including anti-obesity, hypoglycemic, hepatoprotective, anti-fibrotic, anti-inflammatory, anti-tumor, anti-bacterial, anti-fungal, anti-viral, and anti-neurodegenerative activities. These pharmacological effects lay the foundation for its potential application in treating a variety of diseases, though as of the time of the relevant review, these remain areas of research rather than established clinical indications. This evidence is entirely preclinical (cell-culture and animal studies) and cannot be extrapolated to human health claims.
6. Dosage Forms and Reported Dosages
Senna is generally used at a dose of 15 mg of sennosides once daily. The maximum dose is 30 mg of sennosides per day.
Senna is most often used by adults in doses of 17.2 mg sennosides by mouth, once or twice daily.
Pediatric dosages reported in sources:
- Children 2–6 years of age: 4.3 mg once daily; maximum 8.6 mg twice daily.
- Children 6–11 years of age: usually 8.6–15 mg one to two times daily, with a maximum of 17.2 mg twice daily.
- Children younger than 12 years of age should be given senna under medical supervision. Children over 6 years of age may receive one-half the adult dose; children aged 2 to 6 years may receive one-quarter the adult dose. Senna is not to be used by children younger than 2 years of age.
Reported dosages for the powdered drug form are 0.5–3 g; for the liquid extract, 0.5–3 mL.
For bowel cleansing before colonoscopy: a senna fruit dry extract preparation corresponding to 150 mg hydroxyanthracene glycosides (calculated as sennoside B) per single dose has been used in clinical trials. A high dose of senna (3–13 times higher than the recommended dose) is used for cleansing the bowel in preparation for colonoscopy or surgery.
Senna may be administered one to two times daily, but is usually administered as a single dose at bedtime. It should be administered as infrequently as possible at the lowest effective dosage level, and should not be used for more than one week unless directed by a prescriber.
7. Safety Considerations and Drug Interactions
General Safety Profile
Senna is a popular herbal laxative that is available without prescription. It is generally safe and well tolerated, but can cause adverse events including clinically apparent liver injury when used in high doses for longer than recommended periods.
Senna is widely used in fairly low doses without serious problems; it has also been used in a very high dosage form to clear the colon before radiological examination. In this form it is generally well tolerated, but should not be used if there is any predisposition to colonic rupture.
Adverse Effects of Prolonged or High-Dose Use
Other adverse effects include discoloration of the urine and hemorrhoidal congestion. Prolonged use and overdose can result in diarrhea, extreme loss of electrolytes (especially potassium), damage to the surface epithelium, and impairment of bowel function by damage to autonomic nerves.
Overuse can lead to deterioration of normal colonic function, possibly due to the damaging effect that senna has on the myenteric plexus. Senna is possibly unsafe when used for longer than one week or in doses above 34.4 mg sennosides twice daily. Long-term use can cause the bowels to stop functioning normally and might cause dependence on laxatives, as well as liver damage and other harmful effects.
Melanosis Coli and Carcinogenicity Questions
Numerous published studies suggest that long-term use of sennoside A in large doses may have some adverse effects, including the occurrence of melanosis coli and carcinogenesis of colon cancer, thereby limiting its clinical use. It remains to be established whether sennoside A or its metabolites are responsible for the pharmacological and toxicity effects.
The presence of macroscopic or microscopic melanosis coli was not found to be a significant risk factor for the development of adenomas or carcinomas in available research. The authors of that analysis concluded that neither the use of long-term anthranoid laxatives nor melanosis coli were associated with a significant risk of developing colorectal adenoma or carcinoma.
The anthraquinonic glycosides have been described as weak inducers of aberrant crypt foci in the rat colon mucosa and therefore weak promoters of carcinogenesis of rat colon. A 2-year oral gavage study of senna in Sprague-Dawley rats (0, 25, 100, or 300 mg/kg per day) found no treatment-related carcinogenic effects in any target organ, with only slight intestinal hyperplasia in the treated groups. The structure of rhein is chemically similar to danthron, the laxative that was withdrawn from the market due to possible carcinogenic activity in humans. This structural similarity has prompted regulatory attention, though current evidence in animal models at conventional doses does not establish that senna itself is carcinogenic.
Mutagenicity
Mutagenicity testing of sennosides has produced negative results in several bacterial and mammalian systems, except for a weak effect in Salmonella typhimurium strain TA102. No evidence of reproductive toxicity of sennosides has been found in rats and rabbits.
Pregnancy and Lactation
Senna is possibly safe when taken by mouth during pregnancy for up to 1 week. It is possibly unsafe when taken for longer than 1 week or in high doses, which has been linked to serious side effects including laxative dependence and liver damage. The use of senna in pregnancy is considered controversial because senna is a member of the anthraquinone laxatives group, thought to be contraindicated in some situations because overstimulation of the bowel or bladder has the potential to irritate or stimulate the uterus, potentially causing premature labor or miscarriage in the first trimester.
Senna is possibly safe when taken by mouth during breastfeeding for up to 1 week. Small amounts of senna cross into breast milk, but it does not appear to be a problem for nursing babies. As long as senna is used in recommended amounts, it does not cause changes in the babies' stools.
Drug Interactions
Several pharmacologically significant drug interactions have been identified:
- Digoxin: Senna is a stimulant laxative that can decrease potassium levels in the body. Low potassium levels can increase the risk of side effects of digoxin (Lanoxin). The mechanism is increased risk of cardiac toxicity due to potassium depletion.
- Estrogens and hormonal contraceptives: Taking senna might decrease the effects of estrogen. Senna can reduce the amount of estrogen in the body and how much estrogen the body absorbs. Senna can decrease how much estradiol the body absorbs, and taking senna along with certain birth control pills might decrease their effectiveness.
- Diuretics ("water pills"): Some laxatives can cause diarrhea and decrease potassium levels. Diuretics ("water pills") can also decrease potassium levels. Taking senna along with diuretics might make potassium levels drop too low.
- Warfarin: Diarrhea caused by senna can increase the effects of warfarin and increase the risk of bleeding. Excessive amounts of senna should be avoided in patients taking warfarin.
- Kidney and liver disease: Animal research data indicates that senna extract may exert more influence or toxicity on the kidneys and livers, while isolated sennosides show more powerful actions on the colon. The researchers suggest that caution should be particularly exercised in patients with kidney and liver diseases when chronically using senna-based products.
Contraindications Noted in Monographs
Senna is not recommended in patients experiencing a sudden change in bowel movements lasting more than 2 weeks, or presenting with stomach pain, nausea, or vomiting. Because of concerns about its carcinogenicity, senna has been classified as a category III laxative in the United States (indicating safety and effectiveness are not yet fully established).
References
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