Rhein-Anthrone

Rhein-Anthrone at a Glance

Rhein-anthrone (rhein-9-anthrone) is the active laxative principle behind the anthraquinone stimulant laxatives — senna, rhubarb and cascara. Those plants do not contain much of it. What they contain are inactive glycosides — the sennosides (dianthrone diglucosides) and cascarosides — which survive the stomach and small intestine, reach the colon intact, and are there cleaved and reduced by gut bacteria 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 J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. The anthrone is the molecule that actually does the work: it speeds colonic motility and turns the colon from a net absorber of water into a net secretor of it ^{3,7Reference 3Kon 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 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}.

Two features define it and set it apart from its anthraquinone siblings rhein, emodin and chrysophanol. First, it is a reduced anthrone, not an oxidised anthraquinone — and the reduced state is what makes it active. Second, it is chemically unstable: in air it oxidises back to rhein, an anthraquinone that has essentially lost the laxative punch ^{2Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. That instability is the whole story of why rhein-anthrone is discussed as a metabolite rather than sold as a drug — you cannot easily bottle, dose or store the active form.

There is no human trial of isolated rhein-anthrone, and there never will be a clean one: the isolate is the thing that decomposes. Everything human belongs to the parent laxatives, whose stimulant action is well established but whose active-metabolite mechanism was worked out mostly in rodent and isolated-tissue models ^{3,4,5,6Reference 3Kon 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 4Yagi 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 →Reference 5Yagi T et al. · 1991AnimalSuppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in ratsView study →Reference 6Nijs G et al. · 1993Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandinsView study →}.

The Active Laxative Metabolite

This is the point of the molecule, so it is worth stating precisely. The stimulant-laxative mechanism of the whole anthraquinone class routes through rhein-anthrone, and the sequence matters:

1. The plant delivers a prodrug. Senna’s active markers are sennoside A and B — dianthrone diglucosides, each essentially two rhein-anthrone units joined and sugar-capped. They are polar, poorly absorbed, and pharmacologically inert as swallowed ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}.
2. They travel to the colon untouched. Because they are glycosides, the stomach and small intestine neither absorb nor transform them; they arrive in the large intestine intact ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}.
3. Gut bacteria do the activation. Colonic flora cleave the sugars (β-glucosidase) and reduce the liberated dianthrone to two molecules of rhein-anthrone — the active species ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. This bacterial step is obligatory: in germ-free rats, sennosides are not converted and the laxative effect does not appear ^{7Reference 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}.
4. The anthrone stimulates the colon. Rhein-anthrone then acts locally on the colonic wall, producing the two effects that together define stimulant laxation (below).

Why the anthrone, not the glycoside, is the actor. The glycoside is a delivery vehicle: it protects the reactive anthrone through the upper gut and releases it exactly where laxation is wanted. The anthrone is the reactive, membrane-active form — but it is too reactive to survive as a drug substance, which is why the plant (and the formulator) works with the stable glycoside instead. Co-occurring anthrones can even potentiate the effect: a minor aloe-emodin dianthrone from senna, inactive on its own, increased sennoside A’s purgative activity in mice ^{13Reference 13Nakajima 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 →}.

The two colonic actions.

• Prokinetic (motility). Rhein-anthrone stimulates colonic smooth muscle and the peristaltic reflex, accelerating transit so there is less time for water to be reabsorbed. In guinea-pig ileum it produced a dose-dependent, prostaglandin-dependent rise in muscle tension and peristaltic activity ^{6Reference 6Nijs G et al. · 1993Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandinsView study →}.
• Antiabsorptive / secretory. It simultaneously flips the colon’s fluid balance: it reduces net absorption of sodium and chloride and enhances potassium and water secretion, so net water movement shifts from absorption toward net secretion ^{3,7Reference 3Kon 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 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}. Part of this is prostaglandin-E2-mediated — rhein-anthrone raises luminal PGE2, and indomethacin blunts (but does not abolish) its purgative action ^{4,5Reference 4Yagi 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 →Reference 5Yagi T et al. · 1991AnimalSuppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in ratsView study →}. A downstream step involves colonic macrophage activation lowering aquaporin-3 water-channel expression, reducing water reabsorption from the lumen ^{3Reference 3Kon 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 →}. Inhibition of colonic Na⁺/K⁺-ATPase is also part of the antiabsorptive picture for anthrones ^{2Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}.

The instability caveat. Rhein-anthrone is air-sensitive and oxidises to rhein. That is why it is barely present in the finished dried herb, why it is awkward to isolate and study directly, and why the practical control point for the whole system is the glycoside content of the preparation — not any measured amount of the anthrone itself.

Rhein-Anthrone vs. Rhein

These two are a redox pair, and confusing them is the central error to avoid:

• Rhein-anthrone is the reduced 9-anthrone — the active laxative form generated in the colon.
• Rhein is the oxidised anthraquinone — the product rhein-anthrone becomes when it loses electrons to air (or is oxidised in vivo), and it is largely inactive as a laxative ^{2Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}.

So oxidation inactivates the laxative: the anthrone works, the anthraquinone it turns into does not (at least not as a purgative). This has two practical consequences. It explains why free rhein is a poor stand-alone laxative even though it is the more famous, more stable molecule — the free anthraquinone absorbed in the upper gut never reaches the colon as the active anthrone ^{2Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. And it explains why rhein is the species detected in blood, urine and breast milk after a dose of senna: the reactive anthrone does its local work in the colon and the more stable rhein is what survives to circulate and be measured ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. Rhein, uniquely, also has a separate identity as the active metabolite of the osteoarthritis drug diacerein — a systemic story that has nothing to do with rhein-anthrone’s local colonic one (see the rhein page).

What It's Used For

The pharmacology is narrow and coherent: rhein-anthrone is a local colonic stimulant. Its evidence is almost entirely isolated-tissue and rodent mechanism work, with the human efficacy sitting one layer up, in the trials and centuries of use of the parent herbs.

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. All human efficacy is for the parent glycoside-standardised laxatives, not isolated rhein-anthrone (which is too unstable to dose), so the isolate scores reflect mechanistic strength, not standalone human data. Each application links to its write-up.

01Stimulant laxative — colonic motilityPromising52%Established herb effect + isolated-tissue/rodent anthrone mechanism ^{1,6,7Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 6Nijs G et al. · 1993Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandinsView study →Reference 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}

02Antiabsorptive / colonic secretionShaky44%Rodent fluid-transport + PGE2/aquaporin-3 mechanism ^{3,4,7Reference 3Kon 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 4Yagi 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 →Reference 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}

Mechanisms

The load-bearing point: activity lives in the reduced anthrone and is lost on oxidation to rhein — the redox state, not just the carbon skeleton, decides whether the molecule is a laxative.

Pharmacokinetics

The pharmacokinetics are unusual and central to the whole molecule. Rhein-anthrone is not delivered to the colon as itself — it is generated in situ from sennosides by colonic bacteria, so its site of formation and its site of action are the same place ^{1,7Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}. It acts locally; systemic absorption of the intact anthrone is minor. What is absorbed and measured in plasma, urine and breast milk after a senna dose is largely its oxidation product rhein, because the anthrone is short-lived and oxidises readily ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. This has a clean practical implication: there is no meaningful “oral bioavailability of rhein-anthrone” to quote — the active molecule exists transiently at its target and then oxidises away, and the controllable input is the administered glycoside dose, not the anthrone.

Clinical Trials

There are no clinical trials of isolated rhein-anthrone, and its chemistry effectively precludes them — the isolate air-oxidises to inactive rhein. The human clinical record belongs to the parent glycoside-standardised laxatives (senna sennosides and related anthranoids), which are established over-the-counter stimulant laxatives; the long-term-safety literature is likewise at the herb/sennoside level ^{1,10,11Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 10Mitchell JM et al. · 2006AnimalAn oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the ratView study →Reference 11Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Rhein-anthrone pushes the usual isolate-vs-plant caveat to its limit. The isolate essentially cannot be studied as a drug — it is unstable and oxidises to rhein — so the molecule’s evidence is confined to isolated-tissue and rodent mechanism experiments, where it is generated or applied under controlled conditions ^{3,6,7Reference 3Kon 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 6Nijs G et al. · 1993Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandinsView study →Reference 7Van Hoestenberghe A et al. · 1992AnimalThe effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free ratsView study →}. The efficacy evidence is entirely at the whole-herb / glycoside level: senna and its relatives are standardised to sennoside content, and their laxative effect is a herb effect that happens to route through this metabolite. So the honest framing is a two-layer one — the mechanism is rhein-anthrone’s, but the dose, the trials and the safety monitoring all attach to the glycoside-standardised plant, which is the only form anyone actually takes.

Prevalence in Nature

Rhein-anthrone is best described as a metabolite, not a phytochemical: it is largely not stored pre-formed in the intact plant, because free anthrone oxidises to rhein on exposure to air during growth, drying and storage ^{2Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}. What the plants store is the stable, inert glycoside precursors that generate it in the colon:

• Senna (Senna alexandrina / Cassia angustifolia) — leaf and pod, as sennoside A and B (dianthrone diglucosides of rhein-anthrone) plus minor sennosides C/D; pharmacopoeial material is standardised to hydroxyanthracene glycosides expressed as sennoside B (leaf ~2–3%, pod ~3–4%) ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}.
• Rhubarb (Rheum spp.) — rhizome, carrying sennoside-type dianthrone glycosides alongside the free anthraquinones rhein, emodin and chrysophanol.
• Cascara sagrada (Rhamnus purshiana) — bark, whose C-glycosyl cascarosides are the analogous prodrugs (of barbaloin- and chrysophanol-type anthrones rather than rhein specifically).

In every case the same principle holds: the plant supplies a bacterially-activated prodrug, and the active anthrone appears only in the colon. Free rhein-anthrone content in the dried herb is minimal and not a meaningful way to characterise the source.

Discovery & Synthesis

Rhein-anthrone entered the literature not as an isolated natural product but as the answer to a mechanistic question: what does the body make from the sennosides that produces the laxative effect? Twentieth-century anthranoid-laxative research established that the swallowed sennosides are inert and that colonic bacteria reduce them to an active anthrone, rhein-9-anthrone, which is the direct purgative agent ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →}; a precise “first isolation” date is not well documented in the sources reviewed here, reflecting that the molecule was characterised as a transient metabolite rather than a stockpiled compound. Chemically it is the reduced 9-anthrone of rhein (4,5-dihydroxy-anthrone-2-carboxylic acid framework), and the defining synthetic fact is its instability: it oxidises to rhein, so it is handled under controlled reduction rather than bottled. There is no commercial manufacture of rhein-anthrone as such — the article of commerce is the standardised senna/sennoside extract that generates it in vivo; where rhein itself is wanted as a stable reference compound, it is obtained from plant anthraquinones or, industrially, in the diacerein drug lineage (see rhein).

Patents: not yet researched.

Toxicity & Safety

Rhein-anthrone carries a moderate flag, in line with its anthraquinone siblings rhein, emodin and chrysophanol and with its role as the reactive, membrane-active member of the class. The caveats are the stimulant-laxative / anthranoid cautions, applied to the active metabolite.

Safety at a Glance

⚠️ Moderate toxicity

• The class carcinogenicity data are reassuring. A 2-year oral carcinogenicity study of senna in rats found no carcinogenic effect even at high daily doses, and standard genotoxicity batteries on senna, the sennosides and rhein were negative ^{8,10Reference 8Heidemann A et al. · 1993The genotoxicity status of sennaView study →Reference 10Mitchell JM et al. · 2006AnimalAn oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the ratView study →}.
• Stimulant-laxative class risks. Electrolyte loss (especially potassium) with overuse, dependence and reduced bowel tone with chronic daily use, and cramping/griping — the flip side of the motility and secretion it drives.
• Melanosis coli with chronic use. Long-term anthranoid-laxative use pigments the colonic mucosa (lipofuscin in macrophages) from laxative-induced epithelial apoptosis — benign and reversible, and not linked to increased colon-cancer risk, but a marker of sustained use ^{11Reference 11Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →}.
• Regulatory context for the class. Hydroxyanthracene derivatives sit under EU/EFSA scrutiny; the reactive free anthrone is the structural basis for the class genotoxicity concern even though whole-senna and sennoside genotoxicity tests came back negative ^{8,9,12Reference 8Heidemann A et al. · 1993The genotoxicity status of sennaView study →Reference 9Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →Reference 12EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}.

Full Safety & Interactions Detail

Genotoxicity — the reactive-anthrone concern vs the negative herb data. Rhein-anthrone is the reduced, reactive anthrone at the heart of the anthraquinone genotoxicity question, and regulators treat the whole hydroxyanthracene-derivative class cautiously on that structural basis ^{12Reference 12EFSA ANS Panel · 2018Safety of hydroxyanthracene derivatives for use in foodView study →}. Against that, the direct testing has been mostly reassuring: senna, the sennosides and rhein did not increase mutation frequencies across bacterial and mammalian assays (aloe-emodin was the class member showing in-vitro mutagenicity, without in-vivo effect) ^{8Reference 8Heidemann A et al. · 1993The genotoxicity status of sennaView study →}, and a formal assessment concluded the genotoxic risk to patients using senna laxatives is not established ^{9Reference 9Brusick D · 1997Assessment of the genotoxic risk from laxative senna productsView study →}.

Carcinogenicity — negative in the pivotal animal study. A 2-year oral carcinogenicity and toxicity study of Tinnevelly senna fruits in rats found no treatment-related carcinogenic effect in any organ at daily doses up to the high range, with only minor non-neoplastic intestinal and renal changes ^{10Reference 10Mitchell JM et al. · 2006AnimalAn oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the ratView study →}. Chronic use produces melanosis coli — dark colonic pigmentation from laxative-induced epithelial apoptosis and lipofuscin-laden macrophages — which is benign, reversible on stopping, and not associated with increased colorectal-cancer risk ^{11Reference 11Zhang R et al. · 2023ReviewReview on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coliView study →}.

Class laxative cautions. As the active stimulant laxative, rhein-anthrone underlies the familiar anthranoid concerns: potassium and fluid loss with excessive use (which can compound digoxin, diuretic and antiarrhythmic effects), abdominal cramping, and — with habitual daily use — laxative dependence and diminished spontaneous bowel function. These are dose- and duration-driven, tied to the very motility/secretion mechanism above.

Reproductive note (prose only). Stimulant anthranoid laxatives are generally cautioned in pregnancy, and anthraquinone metabolites (notably rhein, the oxidation product that actually circulates) are excreted into breast milk ^{1,2Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →Reference 2Wang J et al. · 2021Pharmacokinetics of anthraquinones from medicinal plantsView study →} — so the systemic exposure of concern is largely rhein’s, not the locally-acting anthrone’s. Consistent with house policy, the pregnancy/lactation decision belongs on the herb or product page where intake is chosen, not on this molecule page; stated here only as the cited finding. No dedicated reproductive-toxicity dataset for isolated rhein-anthrone exists — unsurprisingly, given the isolate’s instability.

Dosage

There is no dose for isolated rhein-anthrone, and there is no coherent way to give one: the molecule is a reactive metabolite that oxidises to inactive rhein, so it is neither formulated nor administered as itself. Human exposure is entirely indirect, through anthranoid laxatives dosed to their glycoside content — senna standardised to sennosides (expressed as sennoside B), rhubarb and cascara to their hydroxyanthracene glycosides ^{1Reference 1Le J et al. · 2021Pharmacology, toxicology, and metabolism of sennoside A, a medicinal plant-derived natural compoundView study →}. For reference only, a common adult over-the-counter senna dose is on the order of 15–30 mg sennosides per day, taken short-term; the amount of rhein-anthrone actually generated depends on the individual’s colonic microbiota, not on a fixed conversion. These are parent-preparation figures for context and are not a personal recommendation — stimulant laxatives are intended for short-term use.

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 J, et al. (2021). Pharmacokinetics of anthraquinones from medicinal plants. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33935728/
3. 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/
4. 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/
5. Yagi T, et al. (1991). Suppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in rats. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/1680171/
6. Nijs G, et al. (1993). Influence of rhein anthrone on peristaltic reflex of guinea-pig isolated ileum: involvement of prostaglandins. British Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/8094026/
7. Van Hoestenberghe A, et al. (1992). The effect of rhein and rhein anthrone on intestinal fluid transport and on large intestine transit in germ-free rats. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/1555634/
8. Heidemann A, Miltenburger HG, Mengs U (1993). The genotoxicity status of senna. Pharmacology. https://pubmed.ncbi.nlm.nih.gov/8234427/
9. 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/
10. 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/
11. 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/
12. EFSA ANS Panel (2018). Safety of hydroxyanthracene derivatives for use in food. EFSA Journal. https://pubmed.ncbi.nlm.nih.gov/32625659/
13. 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/

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