IngredientesSennosides are a class of natural anthraquinone derivatives and dimeric glycosides and are the main bioactive components from medicinal plants used for traditional herbal laxatives, such as Senna alexandrina Mill. Senna alexandrina is the most commonly utilized species for herbal medicine, but has also been classified within the genus Cassia. The two principal commercial source species are Cassia senna L. (Alexandrian or Khartoum senna) and Cassia angustifolia Vahl (Tinnevelly or Indian senna). The genus Senna belongs to the family Fabaceae and comprises about 250–300 accepted species extensively dispersed in tropical and subtropical regions.
"Cassia" derives from the Greek word kasia, meaning "aromatic shrub." The common name "senna" originates from the Arabic word sanaa, meaning "thorny bush," along with sana in Persian and sena in Urdu. Additional plant sources of sennosides include species of rhubarb: sennoside A is a natural dianthrone glycoside mainly from medicinal plants of Senna and rhubarb. Glycosides containing rhein have also been found in Senna reticulata, Rheum rhabarbarum, Rheum palmatum, Aloe vera, and Reynoutria multiflora.
Sennosides are molecules belonging to hydroxyanthracene derivatives (anthraquinone glucosides) present in various botanical species, in particular Cassia angustifolia L., used in medicines and food supplements for their laxative effect. The two primary and most pharmacologically important members of the class are sennoside A (SA) and sennoside B (SB). Sennoside A and its stereoisomer sennoside B are natural anthraquinone derivative and dimeric glycosides.
Sennoside A has the following physicochemical properties: LogP 1.88, molecular formula C42H38O20, molecular weight 862.7, melting point 200–203°C; it is sparingly soluble in methanol, insoluble in water, and displays low bioavailability. Sennoside A can be slowly isomerized to its stereoisomer sennoside B, which has the same molecular formula and an identical substituent (H) located in the opposite direction, in NaHCO3 solution at 80°C.
In the herbal substance, sennosides occur 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. According to the European Pharmacopoeia standard cited by the EMA, the herbal substance contains not less than 2.5 percent of hydroxyanthracene glycosides, calculated as sennoside B (C42H38O20; Mr 863).
Tinnevellin glycoside is found only in Cassia angustifolia Vahl, while 6-hydroxymusizin glycoside is found only in the mature plants of Cassia senna L. — a distinction used to differentiate the two commercial senna species chemically.
Senna is an over-the-counter drug available in multiple formulations, including oral formations (liquid, tablet, and granular) and rectal suppositories. Standard tablet strengths include 8.6, 15, and 25 mg tablets; chewable tablets of 10 and 15 mg; liquid or syrup at 8.8 mg/5 ml; and concentrated oral drops at 8.8 mg/ml. Sennosides are also marketed as standardized whole-leaf or pod powders and as herbal teas. Herbal medicines of the genus Senna prepared by maceration, decoction, infusion, exudates, or stem bath have been commonly used as therapeutic substances.
The medicinal uses of senna have been documented since around the 9th century AD by Arabian physicians. More recently, its residue has been found in Egyptian pottery jars dating to about 3150 BCE. While it is generally consumed today as tea, ancient artifacts suggest senna was preserved and used as an herbal wine, and taken as powders, decoctions, and syrups before that time.
Arabian physicians are credited for bringing senna into the European medical system, and since then, many formulas have been made to round out senna's stimulating effects. Senna was given the name "Purging Cassia" in Europe during the Middle Ages because it was used at that time in an Italian medical school as a purgative.
With such a long history of use, senna-based preparations for occasional constipation are part of the essential pharmacology of many of the great systems of traditional herbal medicine including, among others, Ayurvedic, Traditional Chinese, Unani, and European or Western herbal medicine traditions.
As the most important family member of sennosides, sennoside A is a type of irritant laxative, weight-loss herbal medicine, or dietary supplement which has been routinely used for a long history in China and other Asian countries. In Ayurveda, Ayurvedic practitioners traditionally use the bark and leaves — especially the dried leaflets — for gentle laxative preparations, while the bark finds use in decoctions for fever and inflammation.
The Senna species is widely used in Africa, Asia, Europe, and Latin America; some Senna species are well-known for their antimicrobial and anti-inflammatory activities with basis in traditional medicine to treat diabetes, microbial infections, malaria fever, and other ailments.
Originally this botanical comes from North Africa and still grows natively and commercially in the Nubian region, near the Nile and along the border of Egypt and North Sudan. In the early 20th century, this medicinal herb was brought to the Thar Desert and state of Rajasthan, where the plant is now naturalized and a key crop. India is now the world's largest senna-producing country.
The genus contains important metabolites such as alkaloids, anthraquinones, flavonoids, tannins, glycosides, steroids, terpenoids, saponins, and volatile oils. The primary pharmacologically active constituents are the sennosides themselves, particularly sennoside A and sennoside B, which are dianthrone glycosides. Other anthraquinone-type compounds present include rhein, emodin, aloe-emodin, and chrysophanol, though these occur at lower concentrations and have different individual pharmacological profiles.
Sennosides are pharmacologically inactive prodrugs. Due to their large molecular size and β-glycosidic bonds, they are not absorbed or hydrolyzed in the upper gastrointestinal tract. Their journey begins in the colon, where they are transformed by the resident gut microbiota into their active metabolite, rhein anthrone. This bacterial conversion is essential for the laxative effect, which typically manifests 6 to 12 hours after oral administration, corresponding to the transit time to the colon and subsequent metabolism.
The metabolic cascade is a two-step process initiated by bacterial β-glucosidases, which cleave the sugar moieties from the sennoside molecule to form the aglycones, sennidins. These sennidins are then further reduced by the microbial community to the ultimate active compound, rhein anthrone.
The glycosidic sennosides are not absorbed; they are hydrophilic and do not pass the gastrointestinal tract membranes. The EMA assessment further notes that neither gastric acid nor the α-glycosidase of the small intestine is able to cleave these bonds, confirming that activation occurs exclusively in the large intestine.
Previous studies have identified genera such as Bacteroides and Clostridium as possible contributors to the metabolic conversion process. Differences in bacterial flora may be partly responsible for differences in individual responses to sennoside-based preparations.
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.
Motility effects: The mechanisms of action are firstly an influence on the motility of the large intestine — stimulation of peristaltic contractions and inhibition of local contractions — resulting in accelerated colonic transit, thus reducing fluid absorption. These active compounds stimulate the enteric nervous system in the colon, which increases peristaltic contractions.
Secretory effects: Rhein anthrone inhibits the absorption of water and sodium ions while promoting the secretion of potassium ions and chloride into the colonic lumen. This dual action leads to an increase in the water content of the stool, further facilitating bowel movements.
Aquaporin modulation: The main mechanism by which the SA-derived metabolite, rhein anthrone, inhibits water reabsorption is that it activates macrophages in the colon to secrete prostaglandin E2 (PGE2), which in turn acts as a paracrine factor to downregulate the levels of AQP3 in the epithelia of colon mucosa. The mechanisms were associated with luminal prostanoid level and only partially with cholinergic nerve mediation.
The mechanism of action of sennosides on intestinal motility is a well-defined, dual-pronged process that is entirely dependent on initial metabolic activation by the colonic microbiota.
Senna is approved in the US as a laxative for short-term treatment of constipation. Senna contains many chemicals called sennosides, which irritate the lining of the bowel, causing a laxative effect. Senna is an FDA-approved over-the-counter (OTC) laxative.
Guideline recommendations: The American Gastroenterological Association (AGA) suggests senna over no treatment for chronic idiopathic constipation (conditional recommendation, low certainty of evidence). Research suggests that senna should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration.
Clinical trial data: Shelton (1980) reported that successful treatment of constipation in the immediate postpartum period was achieved in 93% of white patients and 96% of coloured patients in a clinical randomized controlled trial of standardized senna tablets (Senokot®). Pers et al. (1983) treated 20 elderly in-patients (above 60 years old) suffering from severe constipation once daily for 2 weeks with either a preparation containing 15 mg glycoside A+B per sachet or one containing 25 mg glycoside sennae A+B per sachet, and patients were allocated randomly into two treatment groups in a crossover design.
Evidence limitations: While clinical trials used higher doses (1 g daily), this is higher than typically used in clinical practice, and 83% of participants in studies reduced their daily dose. The AGA's classification as a conditional recommendation with low certainty of evidence reflects the limited number of large, rigorous randomized controlled trials on sennosides as monotherapy.
Stimulant laxatives (senna, bisacodyl) increase colonic peristalsis and secretion. They are first-line for opioid-induced constipation (OIC) and effective in immobile patients. Nearly all patients on chronic opioids should receive a stimulant laxative (senna or bisacodyl) ± PEG at opioid initiation.
There is very limited evidence (but much clinical consensus) that sennosides are as effective as lactulose in the management of opioid-induced constipation. This reflects an evidence base largely built on clinical consensus and expert guidelines rather than large-scale double-blind RCTs for this specific indication.
There is no consensus on the "best" management of constipation in palliative care and wide variation in practice between palliative care settings. Systemic absorption of senna or its metabolites is negligible. Combination products with docusate or poloxamer 188 have been used and are still widely used by palliative care services in the UK.
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.
Systematic review evidence in adults: Eleven trials fulfilled the inclusion criteria in a 2022 systematic review and meta-analysis (3,343 patients). Overall, the authors found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% CI]: 1.02 [0.63, 1.67], p = 0.93). This finding suggests that senna achieves comparable bowel cleansing to competing regimens, though the heterogeneity of available studies limits firm conclusions.
Systematic review evidence in children: In total, three randomized controlled trials (318 patients) were identified in a 2021 pediatric meta-analysis. PEG was observed as a preferred protocol of bowel preparation compared with senna (risk ratio [RR] 1.35, 95% CI 1.05–1.74; I² = 15%), and was less painful than senna (RR 0.62, 95% CI 0.44–0.87; I² = 0%). No serious adverse events were noted. Overall, the certainty of the evidence was low to moderate.
Recommendations between U.S. and European guidelines about the use of senna in pre-colonoscopy preparation are unclear.
The following areas represent potential pharmacological activities identified largely in preclinical (in vitro and animal) studies, with little or no confirmed human clinical trial data. Evidence in these domains is preliminary and should be characterized accordingly.
Anti-obesity: Accumulating evidence suggests that sennoside A possesses numerous pharmacological properties, including anti-obesity activity. Sennosides reportedly alleviate the effects of type-2 diabetes and obesity by altering gut microbes. These findings are derived mainly from animal models (HFD-induced obese mice and db/db mice at doses of 25–50 mg/kg in vivo) and have not been confirmed in adequately powered human clinical trials.
Hypoglycemic activity: Accumulating evidence suggests that sennoside A possesses hypoglycemic activity. As with anti-obesity findings, the available data originate from animal studies (streptozotocin-induced diabetic models) and require human confirmation before clinical conclusions can be drawn.
Hepatoprotective and anti-fibrotic effects: Sennoside A has shown hepatoprotective and anti-fibrotic properties in preclinical research. These findings remain at the preclinical stage.
Anti-inflammatory effects: Sennoside A has shown anti-inflammatory activity in preclinical research. The mechanisms under investigation in cell and animal models include modulation of inflammatory cytokines and pathways, but human clinical trial data in inflammatory conditions are absent.
Anti-tumor activity: The anti-tumor property of sennoside A has been demonstrated in diverse tumor models. For instance, SA has been shown to suppress the non-small cell lung cancer cell tumor immune microenvironment and pernicious phenotypes. However, numerous published studies also suggest that long-term use of SA in large doses may have adverse effects, including the occurrence of melanosis coli and carcinogenesis of colon cancer, thereby limiting its clinical use. These contrasting findings underscore the need for human clinical data before any conclusions about anti-cancer utility can be drawn.
Antiviral activity: Sennoside A and B also inhibited HIV-1 ribonuclease H and reverse-transcriptase-associated DNA polymerase activities with IC₅₀ values in the 2–5 µM range. These are in vitro findings only.
Antibacterial and antifungal effects: Other potential therapeutic uses of sennoside A involve antibacterial and antifungal activities. Again, these data come from in vitro and experimental systems, not clinical trials.
Anti-neurodegenerative potential: Sennoside A has many potential pharmacological benefits, including anti-neurodegenerative effects, according to a 2021 review in Frontiers in Pharmacology. Research in this domain is very early stage, primarily conducted in animal models of Alzheimer's disease.
Given that SA is difficult to be absorbed by the gastrointestinal tract, it remains to be determined whether SA itself or its metabolites are responsible for its pharmacological and toxic effects. This fundamental pharmacokinetic uncertainty complicates interpretation of much of the preclinical data.
Senna is most often used by adults in doses of 17.2 mg sennosides by mouth, once or twice daily. Recommended doses in children vary by age.
Evidence-based starting doses from the 2023 AGA-ACG guidelines begin at 8.6–17.2 mg once daily, typically taken at bedtime. Most commercially available senna tablets contain 8–9 mg of sennosides per tablet, and the recommended maximum is 4 tablets twice per day.
For bowel cleansing prior to colonoscopy, considerably higher doses are used: the EMA assessment references a preparation corresponding to 150 mg hydroxyanthracene glycosides, calculated as sennoside B, per single dose for colon cleansing. A clinical comparison study cited by the EMA used sennoside calcium 300 ml of a 1 mg/ml solution given 2 days prior to colonoscopy.
In palliative care for severe constipation, doses may be escalated significantly, with clinical trial protocols studying up to 1 g daily, though 83% of participants in studies reduced their dose from this level due to side effects, indicating that lower doses are typically better tolerated.
Sennosides typically begin to work within 6 to 12 hours after oral administration. This delayed response is due to the time required for the metabolic conversion of sennosides into their active forms, as well as the subsequent physiological processes they instigate within the colon. Sennosides are often taken at bedtime, allowing for a bowel movement the following morning.
In preclinical research, the pharmacological activities of sennoside A have been studied at doses of 30 mg/kg in mice (laxative property, inhibiting contractions in the proximal colon), 50 mg/kg in rats (aquaporin regulation), and 25–50 mg/kg in obese mouse models (anti-obesity effect). These are animal doses and cannot be directly translated to human clinical dosing.
Senna can cause mild abdominal complaints, such as cramps or pain. Other adverse effects are discoloration of the urine and hemorrhoidal congestion. Common side effects of senna glycoside include abdominal cramps. It is not recommended for long-term use, as it may result in poor bowel function or electrolyte problems.
Melanosis coli (MC) is a benign and usually reversible condition characterized by brownish-black pigmentation of the colonic mucosa and is commonly associated with chronic exposure to anthraquinone laxatives. The best-established histopathological sequence involves anthraquinone laxative-related epithelial apoptosis, phagocytosis of apoptotic bodies by macrophages, and subsequent lipofuscin deposition. Although still uncertain, sennoside A may cause melanosis coli and subsequent colon cancer. The potential toxic mechanisms involve aberrant cell proliferation and apoptosis, as well as inflammatory cell infiltration and aberrant crypt foci.
The EFSA ANS Panel reviewed the available scientific data on a possible relationship between hydroxyanthracene derivatives exposure and genotoxic and carcinogenic effects. On the basis of the data currently available, the Panel noted that emodin, aloe-emodin, and the structurally related substance danthron have shown evidence of in vitro genotoxicity.
Considering the possible presence of aloe-emodin and emodin in extracts, the Panel concluded that hydroxyanthracene derivatives should be considered as genotoxic and carcinogenic unless there are specific data to the contrary, such as for rhein, and that there is a safety concern for extracts containing hydroxyanthracene derivatives although uncertainty persists. The Panel was unable to provide advice on a daily intake of hydroxyanthracene derivatives that does not give rise to concerns about harmful effects to health.
In in vivo genotoxicity studies (including micronucleus test with bone marrow cells, chromosome aberration tests with bone marrow cells of rats, and mouse spot tests), the results indicated that senna, fructus sennae extracts, sennosides, and the individual 1,8-dihydroxyanthraquinones tested were uniformly negative. However, the Panel noted that in all these studies, no evidence of toxicity in the target cells was observed, indicating that target tissues may not have been adequately exposed to the test compounds. This methodological caveat is important: the negative in vivo findings do not definitively establish safety, as the colon mucosa (the primary target organ) may not have been adequately characterized in those studies.
Mutagenicity testing of sennosides has produced negative results in several bacterial and mammalian systems, except for a weak effect in Salmonella typhimurium strain TA102.
Long-term use can cause changes in blood electrolytes that can cause heart function disorders, muscle weakness, liver damage, and other harmful effects. Hypokalemia (low serum potassium) is the most clinically relevant electrolyte concern with prolonged or excessive use.
Digoxin: Senna glycosides can increase digoxin toxicity in patients taking digoxin by reducing serum potassium levels, thereby enhancing the effects of digoxin.
Anticoagulants: Diarrhea induced by excessive senna use can increase the effects of warfarin and increase the risk of bleeding. If taking warfarin, excessive amounts of senna should not be taken.
Diuretics: Some laxatives can cause diarrhea and decrease potassium levels. "Water pills" (diuretics) can also decrease potassium levels. Taking senna along with diuretics might make potassium levels drop too low.
Corticosteroids: Corticosteroids such as prednisone may also increase the risk of electrolyte disturbances when combined with senna.
Antibiotics: Similar to other stimulant laxatives, antibiotics may decrease senna's efficacy by affecting the colonic bacteria that produce the active metabolites.
Estrogen: 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.
Stimulant laxatives such as senna are FDA Pregnancy Category C, the category indicating that the drugs had risk on the foetus in animal reproduction studies, but not proven to have an adverse effect on humans in clinical studies. This category of laxative is occasionally prescribed to pregnant women who fail to respond to dietary modifications or to bulking or osmotic laxatives.
Regarding maternal transfer, following the conversion of sennosides to rhein in the mother, the amount of rhein delivered to the infant is very small. Animal experiments demonstrated that placental passage of rhein is small. While no harm has been found to result from use while breastfeeding, such use is not typically recommended.
Absolute contraindications include ileus, intestinal obstruction, severe dehydration, and acute inflammatory bowel conditions. Senna is widely used in fairly low doses without serious problems; however, in high-dosage forms it should not be used if there is any predisposition to colonic rupture. A 15 mg/kg dose is potentially toxic in children under 6 years. Over-the-counter use is not recommended in children under 2 years.
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Sennosides are the active anthraquinone glycoside compounds in senna that are directly responsible for its colon-cleansing laxative effect. They stimulate colonic motility and fluid secretion, and are used in clinical bowel preparation for colonoscopy. RCTs have demonstrated their efficacy in colon cleansing comparable to polyethylene glycol.
Sennosides are the anthraquinone glycoside constituents of senna and rhubarb responsible for their primary laxative action. Metabolized by colonic bacteria to rhein-anthrone, they stimulate propulsive peristalsis and inhibit colonic fluid reabsorption. Multiple pharmacopoeias (WHO, EMA, USP) specify sennoside content as the key quality marker for herbal laxative preparations.
Sennosides are the active anthraquinone glycoside laxative compounds from senna (Alexandrian senna/Cassia senna) responsible for stimulant laxative colon-cleansing action. They are FDA-recognized OTC laxative actives used in whole-body colon cleanse products for bowel evacuation, promoting elimination of intestinal waste.
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