Sennoside C

Sennoside C at a Glance

Sennoside C is one of the four classic dianthrone glycosides of senna (Senna alexandrina / Cassia angustifolia), the family that gives the herb its purgative action. It is the mixed, or hetero, dianthrone: where the dominant sennosides A and B are built from two rhein-anthrone units, sennoside C couples one rhein unit to one aloe-emodin unit ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. Chemically it is a rhein–aloe-emodin heterodianthrone carrying two glucose sugars — a large, polar molecule.

Like all the sennosides it is an inactive prodrug. It is too big and too polar to be absorbed in the small intestine, so it travels intact to the colon, where gut bacteria strip the sugars and split the dianthrone into an active anthrone pair — a rhein-anthrone plus an aloe-emodin anthrone ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. Rhein-anthrone is the molecule that actually does the work of a stimulant laxative: it speeds colonic motility and turns the colon from a net absorber of water into a net secretor of it ^{4,5Reference 4Kon R et al. · 2014Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extractView study →Reference 5Yagi T et al. · 1990AnimalProstaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein anthrone, the active metabolite of sennosides A and B, in the mouse colonView study →}.

The honest headline is that there is essentially no sennoside-C-specific human evidence. It is a minor component of a standardised botanical drug; the clinical record, the pharmacology and the safety data all belong to senna and to the class of hydroxyanthracene laxatives, not to this one heterodianthrone. Everything below is framed accordingly.

The Mixed (Rhein–Aloe-Emodin) Heterodianthrone

The thing that sets sennoside C (and its partner sennoside D) apart from sennosides A and B is what the two halves of the dianthrone are made of.

A dianthrone is two anthrone units joined at their C-10/C-10′ carbons. In senna:

Sennoside	Dianthrone type	The two halves	Stereochemistry
A	Homodianthrone	rhein + rhein	dextrorotatory (the (+) form)
B	Homodianthrone	rhein + rhein	meso (the optically inactive diastereomer of A)
C	Heterodianthrone	rhein + aloe-emodin	dextrorotatory
D	Heterodianthrone	rhein + aloe-emodin	the optically different (meso-type) diastereomer of C

So A/B are a homodimer pair — two identical rhein-anthrone halves — while C/D are the mixed pair, one rhein half and one aloe-emodin half ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. The two chiral centres at C-10 and C-10′ are what generate the A-vs-B and C-vs-D distinction: within each pair, one member is dextrorotatory (sennoside C) and the other is its diastereomer (sennoside D). It is the same structural logic that separates A from B, applied to the mixed dianthrone.

The practical consequence is small but worth stating: because one half is aloe-emodin rather than rhein, bacterial cleavage of sennoside C liberates one rhein-anthrone and one aloe-emodin anthrone, rather than two rhein-anthrones. Rhein-anthrone is the dominant laxative principle either way, so C behaves as a minor purgative sennoside; the aloe-emodin half mainly matters to the safety framing, because aloe-emodin is the anthraquinone in this family that carries the clearest genotoxicity signal (see Toxicity). Sennoside C is a minor co-constituent throughout — the abundant, pharmacopoeially-tracked sennosides are A and B.

What It's Used For

Sennoside C has no dedicated pharmacology of its own in the reviewed literature. What can be said about it is inferred from the shared sennoside-activation pathway and from the well-studied behaviour of sennoside A and its metabolite rhein-anthrone ^{1,2,4,5Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →Reference 4Kon R et al. · 2014Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extractView study →Reference 5Yagi T et al. · 1990AnimalProstaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein anthrone, the active metabolite of sennosides A and B, in the mouse colonView study →}. This section reads the evidence at the level it actually exists — the class and the plant — and flags where sennoside-C-specific data are simply absent.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. No score rests on sennoside C as an isolate; the rows below reflect class/plant-level evidence attributed to it by shared mechanism, so read every row as inherited, not isolate-specific.

01Stimulant laxative (as a senna sennoside)Shaky32%Shared prodrug→rhein-anthrone pathway; established for senna/sennoside A, inherited by C ^{1,2,4,5Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →Reference 4Kon R et al. · 2014Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extractView study →Reference 5Yagi T et al. · 1990AnimalProstaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein anthrone, the active metabolite of sennosides A and B, in the mouse colonView study →}

02Released-aglycone activities (inherited)Shaky18%In-vitro cytotoxic/genotoxic signals of the liberated aloe-emodin & rhein — class data, not sennoside C ^{1,11Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}

Mechanisms

The load-bearing point is that sennoside C is a delivery form, not the active agent: the pharmacology happens after colonic bacteria convert it to rhein-anthrone, exactly as for sennosides A and B ^{1,2,4Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →Reference 4Kon R et al. · 2014Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extractView study →}.

Pharmacokinetics

Sennoside C’s pharmacokinetics are not separately characterised, but the sennoside family behaves as a poorly-absorbed colonic prodrug, and that is the whole point of its design. As a large, doubly-glucosylated dianthrone it is not meaningfully absorbed in the upper gut; it reaches the colon intact, where bacteria cleave it to rhein-anthrone ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. Rhein-anthrone is chemically unstable and air-oxidises to rhein, the anthraquinone that is actually detected in plasma (and, in nursing mothers, in trace amounts in milk) after senna intake ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. So systemic exposure is to rhein, not to the intact sennoside. No sennoside-C-specific absorption, Cmax, half-life or bioavailability figure exists in the sources here; the numbers that exist are for sennoside A and for circulating rhein ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. The low systemic absorption of the parent glycoside is the reassuring part of the profile — the molecule delivers its action locally to the colon rather than distributing through the body.

Clinical Trials

There are no clinical trials of isolated sennoside C. Senna itself is an extensively-used, established OTC stimulant laxative, but its human evidence is for the whole standardised herb (dosed to total sennosides / hydroxyanthracene glycosides), within which sennoside C is a minor, unmeasured component ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. No trial has isolated or dosed sennoside C as an intervention.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule sits at the far plant end of the isolate-vs-plant spectrum. Sennoside C has essentially never been studied as an isolate for efficacy or safety; it is a minor co-constituent of a standardised botanical drug, and all of the usable evidence is at the level of senna or of the hydroxyanthracene class ^{1,9,10,11Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 10Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}. The nearest thing to isolate work in this corner of senna chemistry is a classic study of a related minor dianthrone — a new aloe-emodin dianthrone diglucoside isolated from senna leaf, which had no purgative activity on its own but potentiated the purgative action of sennoside A by about 1.3× in mice ^{3Reference 3Nakajima K et al. · 1985AnimalIsolation of a new aloe-emodin dianthrone diglucoside from senna and its potentiating effect on the purgative activity of sennoside A in miceView study →}. That result is a useful pointer to how minor senna dianthrones behave — as co-actors that modulate the main sennosides rather than as stand-alone drugs — but it is a different molecule, and it should not be read as sennoside-C data. The correct framing is: strong plant-level evidence for senna, shared-mechanism plausibility for sennoside C, and no direct isolate evidence at all.

Prevalence in Nature

Sennoside C is, as far as the reviewed literature goes, a senna-specific minor dianthrone. It occurs alongside sennosides A, B and D in the leaf and pod of senna — both the Alexandrian (Cassia senna / Senna alexandrina) and Tinnevelly/Indian (Cassia angustifolia) drug species, which share sennoside chemistry ^{1,7Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 7Lemli J et al. · 1981Naphthalene glycosides in Cassia senna and Cassia angustifoliaView study →}. Within the plant the sennosides are the purgative-active dianthrone-glycoside fraction, accompanied by naphthalene glycosides (the chemotaxonomic markers tinnevellin glycoside and 6-hydroxymusizin glycoside) and flavonol glycosides such as kaempferol derivatives and rutin ^{7,8Reference 7Lemli J et al. · 1981Naphthalene glycosides in Cassia senna and Cassia angustifoliaView study →Reference 8Ahmed S et al. · 2016Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia VahlView study →}.

Quantitatively, pharmacopoeial senna is standardised to total hydroxyanthracene glycosides, calculated as sennoside B (typically on the order of a few percent of leaf/pod dry weight), and sennoside C is not separately quantified in that standard — it is a small share of the total, dominated by the rhein-homodianthrones A and B ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. No clean, cross-comparable ”% sennoside C” figure is available.

Discovery & Synthesis

The sennosides A and B were the first to be isolated and characterised as senna’s purgative dianthrone glycosides; the mixed heterodianthrones C and D were subsequently identified as the minor rhein–aloe-emodin members of the same family through mid-twentieth-century senna chemistry ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. A precise first-isolation date and author for sennoside C specifically are not well documented in the sources reviewed here.

There is no commercial total synthesis of sennoside C, and no reason for one: it is not a dosed drug. Human exposure comes entirely from senna itself — the dried leaf or pod, or standardised extracts and OTC laxatives prepared from it and calibrated to total sennoside content, within which sennoside C rides along as a minor natural component ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. Manufacture, in other words, is agricultural, not synthetic: grow and standardise the herb.

Patents: not yet researched.

Toxicity & Safety

Sennoside C carries a moderate flag — the same as its active metabolite rhein-anthrone — because it is a member of the anthranoid stimulant-laxative class, and its safety story is that class’s story, not a molecule-specific dataset. The cautions below are hydroxyanthracene-class cautions applied to a minor sennoside.

Safety at a Glance

⚠️ Moderate toxicity

• Low systemic absorption of the intact glycoside. As a large polar diglucoside it acts locally in the colon after bacterial activation, rather than distributing through the body ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang D et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}.
• Stimulant-laxative cautions apply. Not for prolonged or high-dose use: risk of dependence / a “lazy bowel”, fluid-and-electrolyte loss (notably potassium), and abdominal cramping — all class effects of anthranoid laxatives ^{9,11Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}.
• Melanosis coli. Chronic use of anthraquinone laxatives can pigment the colonic lining (a benign, usually reversible discoloration) — a marker of long-term use ^{10Reference 10Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →}.
• The aloe-emodin half feeds the genotoxicity debate. Bacterial cleavage releases aloe-emodin, the anthraquinone with the clearest in-vitro (and some in-vivo) genotoxicity signal, behind the EMA/EFSA restriction on hydroxyanthracene derivatives ^{9,11Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}.
• Pregnancy, lactation and paediatric use are decided at the herb/product level, not here. Stimulant laxatives are generally cautioned in pregnancy, and rhein appears in breast milk in trace amounts — but that judgement belongs on the senna monograph where intake is decided.

Full Safety & Interactions Detail

Class, not molecule. No repeat-dose, reproductive or carcinogenicity study exists for isolated sennoside C. Its risk is inherited from the hydroxyanthracene / anthranoid-laxative class and from senna as a whole ^{9,11Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}.

Stimulant-laxative harms. Prolonged or excessive use of anthranoid laxatives can cause dependence and impaired spontaneous bowel function, fluid and electrolyte disturbances (especially hypokalaemia), and abdominal cramping; short-term, occasional use is the intended pattern ^{9,11Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}. Chronic use is also the setting for melanosis coli, a benign brown pigmentation of the colonic mucosa from anthraquinone-derived pigment, which typically regresses after the laxative is stopped ^{10Reference 10Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →}.

Genotoxicity / carcinogenicity — the class debate. The EFSA panel concluded that hydroxyanthracene derivatives should be treated as genotoxic and carcinogenic unless shown otherwise, singling out aloe-emodin (genotoxic in vivo), emodin and danthron, and could not set a safe intake — prompting EU restriction of these substances in food ^{9Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. Set against that, a dedicated assessment of senna laxatives at prescribed doses did not find a demonstrated genotoxic risk to humans, and a two-year rat study of Tinnevelly-senna fruit found no carcinogenicity at laxative-relevant exposures ^{11,12Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →Reference 12Mitchell JM et al. · 2006AnimalAn oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the ratView study →}. Sennoside C sits inside this unresolved tension: it releases an aloe-emodin unit (feeding the concern) but is a minor fraction of a preparation whose whole-herb data are more reassuring. The page states the debate rather than resolving it.

Reproductive note (prose only). No reproductive-toxicity dataset exists for isolated sennoside C. Stimulant laxatives are generally cautioned in pregnancy; rhein (the circulating metabolite) is excreted into breast milk in small amounts. These pregnancy/lactation decisions belong to the herb or product page where intake is actually decided, not to this molecule page.

Dosage

There is no dose for isolated sennoside C — it is a minor natural component, not a stand-alone product. Human exposure is entirely through senna, which is dosed by its total sennoside / hydroxyanthracene-glycoside content, not by any single sennoside. A common OTC adult senna dose provides roughly 15–30 mg of total sennosides per day (labelled as sennosides, calculated as sennoside B), taken short-term for occasional constipation ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. Within that, sennoside C is a small, unquantified fraction.

The class rule of thumb applies: standardise to sennoside content, use short-term, and avoid prolonged or high-dose use to limit dependence, electrolyte loss and melanosis coli ^{9,10,11Reference 9EFSA ANS Panel (Younes M et al. · 2018Safety of hydroxyanthracene derivatives for use in foodView study →Reference 10Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →Reference 11Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}. These are figures for the whole herb from the literature, not a personal recommendation.

References

1. Le J, et al. (2021). Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compound. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/34764866/
2. Wang D, et al. (2021). Pharmacokinetics of anthraquinones from medicinal plants. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33935728/
3. Nakajima K, Yamauchi K, Kuwano S (1985). Isolation of a new aloe-emodin dianthrone diglucoside from senna and its potentiating effect on the purgative activity of sennoside A in mice. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/2867138/
4. Kon R, et al. (2014). Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/24412547/
5. Yagi T, et al. (1990). Prostaglandin E2-mediated stimulation of mucus synthesis and secretion by rhein anthrone, the active metabolite of sennosides A and B, in the mouse colon. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/1981580/
6. Capasso F, et al. (1983). Effect of indomethacin on aloin and 1,8-dioxyanthraquinone-induced production of prostaglandins in rat isolated colon. Prostaglandins. https://pubmed.ncbi.nlm.nih.gov/6658004/
7. Lemli J, et al. (1981). Naphthalene glycosides in Cassia senna and Cassia angustifolia. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/17402001/
8. Ahmed S, et al. (2016). Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. BMC Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/27835979/
9. EFSA ANS Panel (Younes M, et al.) (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
10. Zhang R, et al. (2023). Review on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coli. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/37214441/
11. Brusick D, Mengs U (1997). Assessment of the genotoxic risk from laxative senna products. Environmental and Molecular Mutagenesis. https://pubmed.ncbi.nlm.nih.gov/9020301/
12. Mitchell JM, et al. (2006). An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat. Archives of Toxicology. https://pubmed.ncbi.nlm.nih.gov/16205914/

View all 12 references▾