Fructus Sennae consists of the dried ripe fruit of Cassia senna L. (Fabaceae).1
1 Cassia italica Mill. is listed in the Malian pharmacopoeia.
Fabaceae are also referred to as Leguminosae.
Cassia acutifolia Delile and Cassia angustifolia Vahl. (1) are recognized as two distinct species in a number of pharmacopoeias as Alexandrian senna fruit and Tinnevelly senna fruit (2–7). Botanically, however, they are considered to be synonyms of the single species Cassia senna L. (1).
Selected vernacular names
Alexandria senna, Alexandrian senna, cassia, eshrid, falajin, fan xie ye, filaskon maka, hindisana, illesko, Indian senna, ma khaam khaek, makhaam khaek, Mecca senna, msahala, nelaponna, nelatangedu, nilavaka, nilavirai, nubia senna, rinji, sanai, sand hijazi, sanjerehi, sen de Alejandria, sen de la India, senna makki, senna, senna pod, senamikki, sona-mukhi, Tinnevelly senna, true senna (8–11).
Low shrubs, up to 1.5 m high, with compound paripinnate leaves, having 3–7 pairs of leaflets, narrow or rounded, pale green to yellowish green. Flowers, tetracyclic, pentamerous and zygomorphic, have quincuncial calyx, a corolla of yellow petals with brown veins, imbricate ascendent prefloration, and a partially staminodial androeceum. The fresh fruit is a broadly elliptical, somewhat reniform, flattened, parchment-like, dehiscent pod, 4–7 cm long by 2cm wide, with 6–10 seeds (9, 12, 13).
Plant material of interest: dried ripe fruit
Fructus Sennae is leaf-like, has flat and thin pods, yellowish green to yellowish brown with a dark brown central area, oblong or reniform. Fruit is pale to greyish green, 3.5–6.0 cm in length, 1.4–1.8 cm in width; stylar point at one end, containing 6–10 obovate green to pale brown seeds with longitudinal prominent ridges on the testa (2).
Colour is pale green to brown to greyish black (2, 3); odour, characteristic; taste, mucilaginous and then slightly bitter (2).
Epicarp with very thick cuticularized isodiametrical cells, occasional anomocytic or paracytic stomata, and very few unicellular and warty trichomes; hypodermis with collenchymatous cells; mesocarp with parenchymatous tissue containing a layer of calcium oxalate prisms; endocarp consisting of thick-walled fibre, mostly perpendicular to the longitudinal axis of the fruit, but the inner fibres running at an oblique angle or parallel to the longitudinal axis. Seeds, subepidermal layer of palisade cells with thick outer walls; the endosperm has polyhedral cells with mucilaginous walls (2).
Powdered plant material
Brown; epicarp with polygonal cells and a small number of conical warty trichomes and occasional anomocytic or paracytic stomata; fibres in two crossed layers accompanied by a crystal sheath of calcium oxalate prisms; characteristic palisade cells in the seeds and stratified cells in the endosperm; clusters and prisms of calcium oxalate (4).
The plant is indigenous to tropical Africa. It grows wild near the Nile river from Aswan to Kordofan, and in the Arabian peninsula, India, and Somalia (12, 13). It is cultivated in India, Pakistan, and the Sudan (8, 9, 11–14).
General identity tests
Macroscopic, microscopic, and microchemical examinations (2–7), and thinlayer chromatographic analysis for the presence of characteristic sennosides (sennosides A–D).
The test for Salmonella spp. in Fructus Sennae products should be negative. The maximum acceptable limits of other microorganisms are as follows (15–17). For preparation of decoction: aerobic bacteria-107/g; moulds and yeast-105/g; Escherichia coli-102/g; other enterobacteria-104/g. Preparations for internal use: aerobic bacteria-105/g or ml; moulds and yeast-104/g or ml; Escherichia coli- 0/g or ml; other enterobacteria-103/g or ml.
Foreign organic matter
Not more than 1.0% (2).
Not more than 6% (3).
Not more than 2.0% (2, 4, 5).
Not less than 25% (2).
Not more than 12% (5).
To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Fructus Sennae is not more than 0.05 mg/kg (17). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (15) and guidelines for predicting dietary intake of pesticide residues (18).
Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (15).
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (15).
Other purity tests
Chemical tests and tests of alcohol-soluble extractive to be established in accordance with national requirements.
Contains not less than 2.2% of hydroxyanthracene glycosides, calculated as sennoside B (2–7). Quantitative analysis is performed by spectrophotometry (2, 5–7) or by high-performance liquid chromatography (19).
The presence of sennosides A and B (3–5) can be determined by thin-layer chromatography.
Major chemical constituents
Fructus Sennae contains a family of hydroxyanthracene glycosides, the most plentiful of which are sennosides A and B (for structures, see page 244). There are also small amounts of aloe-emodin and rhein 8-glucosides, mucilage, flavonoids, and naphthalene precursors (12, 13, 20).
Crude plant material, powder, oral infusion, and extracts (liquid or solid, standardized for content of sennosides A and B) (12, 20, 21). Package in wellclosed containers protected from light and moisture (2–7).
Uses supported by clinical data
Short-term use in occasional constipation (21–25).
Uses described in pharmacopoeias and in traditional systems of medicine
Uses described in folk medicine, not supported by experimental or clinical data
As an expectorant, a wound dressing, an antidysenteric, and a carminative agent; and for the treatment of gonorrhoea, skin diseases, dyspepsia, fever, and haemorrhoids (11, 23, 25).
The effects of Fructus Sennae are due primarily to the hydroxyanthracene glucosides, especially sennosides A and B. These β-linked glucosides are secretagogues that induce net secretion of fluids, and specifically influence colonic motility and enhance colonic transit. They are not absorbed in the upper intestinal tract; they are converted by the bacteria of the large intestine into the active derivatives (rhein-anthrone). The mechanism of action is twofold: an effect on the motility of the large intestine (stimulation of peristaltic contractions and inhibition of local contractions), which accelerates colonic transit, thereby reducing fluid absorption; and an influence on fluid and electrolyte absorption and secretion by the colon (stimulation of mucus and active chloride secretion), which increases fluid secretion (24, 25).
The time of action of Senna is usually 8–10 hours, and thus the dose should be taken at night (24). The action of the sennosides augments, without disrupting, the response to the physiological stimuli of food and physical activity (24). The sennosides abolish the severe constipation of patients suffering from severe irritable bowel syndrome (26). In therapeutic doses, the sennosides do not disrupt the usual pattern of defecation times and markedly soften stools (24). Sennosides significantly increase the rate of colonic transit (27) and increase colonic peristalsis, which in turn increases both faecal weight and dry bacterial mass (24, 28). Due to their colonic specificity, the sennosides are poorly absorbed in the upper gastrointestinal tract (29).
The major symptoms of overdose are griping and severe diarrhoea with consequent losses of fluid and electrolytes. Treatment should be supportive with generous amounts of fluid. Electrolytes, particularly potassium, should be monitored, especially in children and the elderly.
As with other stimulant laxatives, the drug is contraindicated in cases of ileus, intestinal obstruction, stenosis, atony, undiagnosed abdominal symptoms, in- flammatory colonopathies, appendicitis, abdominal pains of unknown cause, severe dehydration states with water and electrolyte depletion, or chronic constipation (20, 21, 30). Fructus Sennae should not be used in children under the age of 10 years.
Stimulant laxative products should not be used when abdominal pain, nausea, or vomiting are present. Rectal bleeding or failure to have a bowel movement after use of a laxative may indicate a serious condition (31). Chronic abuse with diarrhoea and consequent fluid and electrolyte losses may cause dependence and need for increased dosages, disturbance of the water and electrolyte balance (e.g. hypokalaemia), atonic colon with impaired function and albuminuria and haematuria (21, 32).
The use of stimulant laxatives for more than 2 weeks requires medical supervision.
Chronic use may lead to pseudomelanosis coli (harmless).
Hypokalaemia may result in cardiac and neuromuscular dysfunction, especially if cardiac glycosides (digoxin), diuretics, corticosteroids, or liquorice root are taken (29).
Use for more than 2 weeks requires medical attention (21, 31).
Decreased intestinal transit time may reduce absorption of orally administered drugs (32, 33).
The increased loss of potassium may potentiate the effects of cardiotonic glycosides (digitalis, strophanthus). Existing hypokalaemia resulting from longterm laxative abuse can also potentiate the effects of antiarrhythmic drugs, such as quinidine, which affect potassium channels to change sinus rhythm. Simultaneous use with other drugs or herbs which induce hypokalaemia, such as thiazide diuretics, adrenocorticosteroids, or liquorice root, may exacerbate electrolyte imbalance (20, 21).
Drug and laboratory test interactions
Urine discoloration by anthranoid metabolites may lead to false positive test results for urinary urobilinogen and for estrogens measured by the Kober procedure (32).
Carcinogenesis, mutagenesis, impairment of fertility
No in vivo genotoxic effects have been reported to date (34–37). Although chronic abuse of anthranoid-containing laxatives was hypothesized to play a role in colorectal cancer, no causal relationship between anthranoid laxative abuse and colorectal cancer has been demonstrated (38–40).
Pregnancy: non-teratogenic effects
Use during pregnancy should be limited to conditions in which changes in diet or fibre laxatives are not effective (41).
Use during breast-feeding is not recommended owing to insufficient available data on the excretion of metabolites in breast milk (21). Small amounts of active metabolites (rhein) are excreted into breast milk, but a laxative effect in breastfed babies has not been reported (21).
Contraindicated for children under 10 years of age (21).
No information available concerning teratogenic effects on pregnancy.
Senna may cause mild abdominal discomfort such as colic or griping (21, 22, 33). A single case of hepatitis has been described after chronic abuse (42). Melanosis coli, a condition which is characterized by pigment-loaded macrophages within the submucosa, may occur after long-term use. This condition is clinically harmless and disappears with cessation of treatment (33, 43, 44).
Long-term laxative abuse may lead to electrolyte disturbances (hypokalaemia, hypocalcaemia), metabolic acidosis or alkalosis, malabsorption, weight loss, albuminuria, and haematuria (21, 22, 33). Weakness and orthostatic hypotension may be exacerbated in elderly patients who repeatedly use stimulant laxatives (21, 33). Conflicting data exist on other toxic effects such as intestinal-neuronal damage after long-term misuse (45–54).
The correct individual dose is the smallest required to produce a comfortable, soft-formed motion (21). Powder, 1–2g of fruit daily at bedtime (8, 19, 20). Adults and children over 10 years: standardized daily dose equivalent to 10– 30mg sennosides (calculated as sennoside B) taken at night.
1. Brenan JPM. New and noteworthy Cassia from tropical Africa. Kew bulletin, 1958, 13:231–252.
2. The international pharmacopoeia, 3rd ed. Vol. 3. Quality specifications. Geneva, World Health Organization, 1988.
3. African pharmacopoeia, 1st ed. Lagos, Organization of African Unity, Scientific, Technical & Research Commission, 1985.
4. British pharmacopoeia. London, Her Majesty's Stationery Office, 1993.
5. European pharmacopoeia, 2nd ed. Strasbourg, Council of Europe, 1995.
6. Deutsches Arzneibuch 1996. Stuttgart, Deutscher Apotheker Verlag, 1991.
7. Pharmacopée française. Paris, Adrapharm, 1996.
8. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, March 15, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).
9. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, Blakiston, 1950.
10. Medicinal plants of India, Vol. 1. New Delhi, Indian Council of Medical Research, 1976.
11. Huang KC. The pharmacology of Chinese herbs. Boca Raton, FL, CRC Press, 1994.
12. Farnsworth NR, Bunyapraphatsara N, eds. Thai medicinal plants. Bangkok, Prachachon, 1992.
13. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.
14. Tyler VE, Brady LR, Robbers JE, eds. Pharmacognosy, 9th ed. Philadelphia, Lea & Febiger, 1988.
15. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.
16. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.
17. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.
18. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).
19. Duez P et al. Comparison between high-performance thin-layer chromatography- fluorometry and high-performance liquid chromatography for the determination of sennosides A and B in Senna (Cassia spp.) pods and leaves. Journal of chromatography, 1984, 303:391–395.
20. Bisset NG. Max Wichtl's herbal drugs and phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.
21. Core-SPC for Sennae Fructus Acutifoliae/Fructus Angustifoliae. Coordinated review of monographs on herbal remedies. Brussels, European Commission, 1994.
22. German Commission E Monograph, Senna fructus. Bundesanzeiger, 1993, 133:21 July.
23. Leng-Peschlow E. Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat. Journal of pharmacy and pharmacology, 1986, 38:606–610.
24. Godding EW. Laxatives and the special role of Senna. Pharmacology, 1988, 36(Suppl. 1):230–236.
25. Bradley PR, ed. British herbal compendium, Vol. 1. Bournemouth, British Herbal Medicine Association, 1992.
26. Waller SL, Misiewicz JJ. Prognosis in the irritable-bowel syndrome. Lancet, 1969, ii:753–756.
27. Ewe K, Ueberschaer B, Press AG. Influence of senna, fibre, and fibre + senna on colonic transit in loperamide-induced constipation. Pharmacology, 47(Suppl. 1):242– 248.
28. Stephen AM, Wiggins HS, Cummings JH. Effect of changing transit time on colonic microbial metabolism in man. Gut, 1987, 28:610.
29. Goodman and Gilman's the pharmacological basis of therapeutics, 9th ed. New York, McGraw-Hill, 1996.
30. Physicians' desk reference, 49th ed. Montvale, NJ, Medical Economics Company, 1995.
31. American hospital formulary service. Bethesda, MD, American Society of Hospital Pharmacists, 1990.
32. United States pharmacopeia, drug information. Rockville, MD, US Pharmacopeial Convention, 1992.
33. Reynolds JEF, ed. Martindale, the extra pharmacopoeia, 30th ed. London, Pharmaceutical Press, 1993.
34. Heidemann A, Miltenburger HG, Mengs U. The genotoxicity of Senna. Pharmacology, 1993, 47(Suppl. 1):178–186.
35. Tikkanen L et al. Mutagenicity of anthraquinones in the Salmonella preincubation test. Mutation research, 1983, 116:297–304.
36. Westendorf et al. Mutagenicity of naturally occurring hydroxyanthraquinones. Mutation research, 1990, 240:1–12.
37. Sanders D et al. Mutagenicity of crude Senna and Senna glycosides in Salmonella typhimurium. Pharmacology and toxicology, 1992, 71:165–172.
38. Lyden-Sokolowsky A, Nilsson A, Sjoberg P. Two-year carcinogenicity study with sennosides in the rat: emphasis on gastrointestinal alterations. Pharmacology, 1993, 47(Suppl. 1):209–215.
39. Kune GA. Laxative use not a risk for colorectal cancer: data from the Melbourne colorectal cancer study. Zeitschrift für Gasteroenterologie, 1993, 31:140–143.
40. Siegers CP. Anthranoid laxatives and colorectal cancer. Trends in pharmacological sciences (TIPS), 1992, 13:229–231.
41. Lewis JH et al. The use of gastrointestinal drugs during pregnancy and lactation. American journal of gastroenterology, 1985, 80:912–923.
42. Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of Senna. Lancet, 1991, 337:472.
43. Loew D. Pseudomelanosis coli durch Anthranoide. Zeitschrift für Phytotherapie, 1994, 16:312–318.
44. Müller-Lissner SA. Adverse effects of laxatives: facts and fiction. Pharmacology, 1993, 47(Suppl. 1):138–145.
45. Godding EW. Therapeutics of laxative agents with special reference to the anthraquinones. Pharmacology, 1976, 14(Suppl. 1):78–101.
46. Dufour P, Gendre P. Ultrastructure of mouse intestinal mucosa and changes observed after long term anthraquinone administration. Gut, 1984, 25:1358–1363.
47. Dufour P et al. Tolérance de la muqueuse intestinale de la souris à l'ingestion prolongée d'une poudre de sené. Annales pharmaceutiques françaises, 1983, 41(6):571– 578.
48. Kienan JA, Heinicke EA. Sennosides do not kill myenteric neurons in the colon of the rat or mouse. Neurosciences, 1989, 30(3):837–842.
49. Riemann JF et al. Ultrastructural changes of colonic mucosa in patients with chronic laxative misuse. Acta hepato-gastroenterology, 1978, 25:213–218.
50. Smith BA. Effect of irritant purgatives on the myenteric plexus in man and the mouse. Gut, 1968, 9:139–143.
51. Riemann JF et al. The fine structure of colonic submucosal nerves in patients with chronic laxative abuse. Scandinavian journal of gastroenterology, 1980, 15:761–768.
52. Rieken EO et al. The effect of an anthraquinone laxative on colonic nerve tissue: A controlled trial in constipated women. Zeitschrift für Gasteroenterologie, 1990, 28:660– 664.
53. Riemann JF, Schmidt H. Ultrastructural changes in the gut autonomic nervous system following laxative abuse and in other conditions. Scandinavian journal of gastroenterology, 1982, 71(Suppl.):111–124.
54. Krishnamurti S et al. Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology, 1985, 88:26–34.