IngredientsDianthrone (also written as dianthrone or referred to by its systematic name) is a polycyclic aromatic compound formed by the coupling of two anthrone units. Its IUPAC name is (9,9′-Bianthracene)-10,10′(9H,9′H)-dione, with synonyms including bianthronyl, 10,10′-bianthrone, and 10,10′-dianthronyl; its CAS Registry Numbers include 434-84-4 and 472-29-7. Its molecular formula is C₂₈H₁₈O₂ and it is catalogued in PubChem under Compound ID (CID) 97174.
From a scientific perspective, dianthrones are classified as anthraquinone derivatives. The structural class is defined by a carbon–carbon bond linking two anthrone halves at the C-9/C-9′ position, yielding a highly conjugated dimeric framework. In nature, dianthrones rarely occur as the free aglycone; they are most commonly encountered as O-glycosides or C-glycosides, in which sugar residues are attached to the dimer.
A pharmacologically and structurally distinct subclass, the naphthodianthrones, exists within the broader dianthrone family. Hypericin is a naphthodianthrone, a red-colored anthraquinone-derivative, which, together with hyperforin, is one of the principal active constituents of St. John's Wort (Hypericum perforatum). Hypericin and pseudohypericin are two natural products, structurally belonging to the chemical class of naphthodianthrones and the characteristic constituents of the genus Hypericum (Clusiaceae).
The term "dianthrone" in dietary supplement contexts most commonly refers to one of two distinct groups of naturally occurring compounds:
Dianthrone is a naturally occurring compound found primarily in certain species of the Rheum (rhubarb) and Cassia plants, both of which have a long-standing history of use in traditional herbal medicine. Sennoside A is a natural dianthrone glycoside mainly from medicinal plants of Senna and Rhubarb.
The principal plant sources confirmed by peer-reviewed phytochemical research include:
Senna contains anthraquinones, including dianthrone glycosides (1.5% to 3%), sennosides A and B (rhein dianthrones), and sennosides C and D (rhein aloe-emodin heterodianthrones). Numerous minor sennosides have been identified and contribute to senna's laxative effect. The plant also contains free anthraquinones in small amounts, including rhein, aloe-emodin, chrysophanol, and their glycosides. Senna pods contain the same rhein dianthrone glycosides as the leaves.
In the case of St. John's Wort, the reddish dianthrone pigment hypericin (Hypericum red) ranges from 0.02% to 2.5%, depending on harvesting period, drying process, and storage. Hypericin content varies widely among growing regions, and concentrations are contingent on plant part, with flowers, buds, top leaves, and secondary stems yielding the highest percentages. Preparations vary greatly in chemical content and quality, and may be standardized regarding quantity of hyperforin (commonly 3% to 5%) or hypericin (commonly 0.3%) constituents.
Naphthodianthrones exist in various forms in Hyperici herba. Protopseudohypericin and protohypericin (protopigments) are converted into pseudohypericin and hypericin (pigments) under the action of light.
Dianthrone-containing preparations encountered in dietary supplement and pharmaceutical contexts include: standardized dried leaf or pod powders of Senna; aqueous, hydroalcoholic, and ethanolic root extracts of Polygonum multiflorum (processed and raw forms); standardized Hypericum perforatum extracts; rhubarb root extracts; and isolated or semi-purified sennoside concentrates used in pharmaceutical laxative formulations.
In traditional Chinese medicine (TCM), dianthrone derivatives from rhubarb roots (such as rhein dianthrone and sennoside dianthrones) have been utilized as potent remedies for digestive health, chiefly for their mild laxative effects. They were commonly prescribed to alleviate constipation, promote bowel regularity, and detoxify the digestive tract, thus supporting overall wellness.
The roots of Polygonum multiflorum Thunb. are used as a traditional Chinese medicinal herb to treat many diseases. They are applied as remedies for preventing hair loss and premature graying, strengthening bones and muscles, and treating seminal emission and menstrual and menopausal complaints. Polygonum multiflorum Thunb. is a traditional Chinese medicine with pharmacological activities such as anti-inflammatory, anti-oxidation and anti-aging.
Historically, senna and rhubarb have been valued for their laxative properties, with dianthrone derivatives such as sennosides and rheinosides being recognized as active constituents responsible for their effects. In traditional Chinese and Ayurvedic medicine, preparations containing dianthrone-rich extracts have been used to support digestive health and relieve occasional constipation.
Historically, dianthrone-rich botanicals were also employed in remedies addressing inflammation and supporting liver function. Their use extended to herbal poultices and infusions aimed at reducing swelling and promoting the healing of minor wounds.
Plants of the Hypericum genus (comprising approximately 450 species) are widely distributed all around the world and have been used since antiquity for a range of medicinal properties. The use of H. perforatum as a wound herb, mood stabilizer, and nerve tonic in European folk medicine long predates the identification of its naphthodianthrone content.
Polygonum sp. (Polygonaceae) is used in traditional Turkish medicine for treating rheumatic pain, eczema, inflamed wounds, abdominal pain, and anemia.
Within the dianthrone chemical class, several structurally distinct compounds have been the focus of phytochemical and pharmacological research:
Sennosides are a class of natural anthraquinone derivatives and dimeric glycosides. Sennoside A and B (SA, SB) are the main purgative components; two further pharmacologically active sennosides, sennoside C and D (SC, SD), were later isolated from the same plant.
Sennoside A has the following physicochemical properties: LogP 1.88, molecular formula C₄₂H₃₈O₂₀, molecular weight 862.7 g/mol, melting point 200–203°C, sparingly soluble in methanol, insoluble in water, and low bioavailability.
Six principal dianthrones identified in P. multiflorum are: trans-emodin-emodin dianthrones (1), cis-emodin-emodin dianthrones (2), trans-emodin-physcion dianthrones (3), cis-emodin-physcion dianthrones (4), trans-physcion-physcion dianthrones (5), and cis-physcion-physcion dianthrones (6).
Seven new dianthrone glycosides, named polygonumnolides A1–B3 (1–7), were isolated from the 70% EtOH extract of the dried roots of Polygonum multiflorum Thunb. using column chromatography and preparative high-performance liquid chromatography; their structures were determined by 1D and 2D NMR and mass spectroscopy.
The most common classes of active compounds in H. perforatum include naphthodianthrones, phloroglucinols, and flavonoids. Two major active constituents have been identified: hypericin (a naphthodianthrone) and hyperforin (a phloroglucinol). Due to its chemical structure, hypericin is highly photoreactive. Biochemically, hypericin is a polycyclic quinone, possessing four hydroxyl groups positioned adjacent to two carbonyl groups.
The laxative pharmacology of sennoside dianthrones is one of the most thoroughly characterized mechanisms among any plant-derived natural products.
Sennosides, naturally occurring dianthrone glycosides derived from the Senna plant, are widely utilized as stimulant laxatives for the treatment of constipation. Their pharmacological activity is not direct but relies on a complex series of metabolic and physiological events within the lower gastrointestinal tract.
Step 1 — Prodrug activation by gut microbiota: When ingested, sennosides remain largely inactive as they pass through the stomach and small intestine. It is only upon reaching the colon that sennosides are metabolized by the intestinal flora into their active aglycone form, rhein anthrone. This transformation is crucial for the pharmacological effects of sennosides.
Step 2 — Dual action of the active metabolite rhein anthrone: 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; secondly, there is an influence on secretion processes.
Rheinanthrone directly stimulates submucosal sensory neurons and myenteric plexus activity, upregulates cyclooxygenase-2 (COX-2) expression in intestinal macrophages, and increases prostaglandin E2 (PGE2) production, collectively enhancing propulsive peristaltic contractions. Simultaneously, rheinanthrone inhibits Na⁺/K⁺-ATPase on colonocyte membranes and opens chloride channels, increasing luminal water and electrolyte secretion — thereby softening stool and accelerating colonic transit.
A study showed that sennoside A (30 mg/kg) inhibited contractions in the proximal colon, reduced the passage time of luminal contents, and reduced the absorption of water, resulting in accelerated transit of luminal contents in the distal colon. These mechanisms were associated with luminal prostanoid levels and only partially with cholinergic nerve mediation. Additionally, sennoside A (50 mg/kg) decreased the colonic expression of aquaporins (AQPs), thereby inhibiting lumen-to-blood water transportation and leading to defecation.
The combination of augmented peristalsis and altered fluid dynamics results in a laxative effect that typically manifests within 6 to 12 hours after oral administration.
Among emodin dianthrone analogs, trans-emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. A dianthrone-rich fraction (Fraction D) of P. multiflorum showed potent PTP1B inhibitory activity (inhibition rate: 98.4% at 10 μg/mL, IC₅₀: 1.27 ± 0.11 μg/mL). PTP1B is a key negative regulator of insulin receptor signaling-related tyrosine phosphorylation.
Evidence level: Multiple randomized controlled trials in humans; strong for short-term use.
The EMA and ESCOP recommend short-term use of senna to treat occasional constipation. Senna, in accordance with the European Pharmacopoeia monograph, must contain at least 2.5% hydroxyanthracene glycosides calculated as sennoside B, relative to the dried plant.
A small study in middle-aged adults with chronic idiopathic constipation showed that 500 mg of senna taken twice daily for 4 weeks was as effective as 500 mg of magnesium oxide taken three times daily.
In adults, a clinical trial compared a standardized senna preparation at a dose of 11 grams (0.7 grams of active ingredient, about one-third of the pharmacopoeial maximum) and found it to be an effective laxative.
For geriatric patients, a dose of 20 mg sennoside B, taken twice daily for 28 days, was shown to be effective and well-tolerated, with fewer side effects compared to combination therapy with bisacodyl.
In pediatric patients with constipation related to anorectal malformations, the maximum daily dose of senna (sennosides A and B) used was 38.7 mg, with no adverse effects reported; this dosage was found to be effective and safe for children in a controlled clinical setting.
For chronic idiopathic constipation, the American Gastroenterological Association suggests senna over no treatment (conditional recommendation, low certainty evidence).
Evidence level: Preclinical (animal/in vitro) only; no established human clinical evidence for weight management.
Several reports found that sennoside A might decrease energy intake from the intestine by accelerating transit of luminal contents in the distal colon. Moreover, sennoside A was reported to be a common ingredient in both herbal medicines and dietary supplements for weight-loss.
Sennosides reportedly alleviate the effects of type-2 diabetes and obesity by altering gut microbes. These findings derive from animal models and in vitro experiments; no rigorous human randomized controlled trials have specifically evaluated dianthrone preparations for obesity as a primary endpoint.
Evidence level: Preclinical only; in vitro and animal models.
Sennoside A showed antiviral activity against human immunodeficiency virus type 1 (HIV-1), as well as anti-inflammatory, antioxidant, and antidiabetic effects, with protective action against liver cirrhosis. These findings are from preclinical studies. The anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb. has been explored; among these analogs, trans-emodin dianthrone enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice.
Evidence level: In vitro and animal studies; no controlled human trials specifically on dianthrone constituents.
Accumulating evidence suggests that sennoside A possesses numerous pharmacological properties, including anti-inflammatory, among other activities. Research on Polygonum species has revealed anti-inflammatory, antidiabetic, neuroprotective, and antidiarrheal properties. All reported anti-inflammatory data remain preclinical.
Evidence level: In vitro and early preclinical; no established clinical evidence.
Other potential therapeutic uses of sennoside A involve antibacterial and antifungal activities, including the use of this compound as capped silver nanoparticles. Antiviral activity including against HIV-1 has been noted in preclinical work, but these observations have not been translated into human clinical studies for dianthrone compounds specifically.
Evidence level: In vitro/cell-line studies; no human clinical evidence.
Isolated polygonumnolide dianthrone glycosides were evaluated for their cytotoxic effects against KB tumor cell lines and compounds 1–4 showed moderate cytotoxicity. Sennoside A has been reported to possess anti-tumor properties in preclinical models. These results are entirely derived from cell-line work and are at a very early exploratory stage.
Evidence level: Multiple human RCTs for St. John's Wort extracts as a whole; the specific contribution of the naphthodianthrone fraction to antidepressant effects is not clearly established.
Naphthodianthrone hypericin and the phloroglucinol derivative hyperforin act on neurotransmitters to regulate mood. Initially, hypericin was thought to be the dominant ingredient for antidepressant effects; however, more recently, hyperforin has also been identified as having these effects.
Clinical trials evaluating the efficacy of St. John's Wort in depression have commonly used 900 mg of extract daily in 3 divided doses for up to 12 weeks (range, 200 to 1,800 mg/day). It is important to note that these trials tested the whole standardized extract, not isolated naphthodianthrones; thus, isolating the specific contribution of the dianthrone fraction from the total extract evidence is not currently possible.
Dianthrone-containing preparations are available in many forms, and dosages reported in studies vary considerably depending on the plant source, preparation, and indication. The following dosages are drawn directly from published sources:
Melanosis coli (MC) is usually caused by the long-term use of anthraquinone laxatives, such as senna, rhubarb, aloe, rhamnus, and frangula. MC, which is common in people who suffer from long-term constipation, is a benign, reversible entity and can be gradually improved over one year after stopping the use of laxatives. Anthraquinones cause direct injury to and apoptosis of the colonic epithelial cells, resulting in lipofuscin deposition in the macrophages of the lamina propria, visible as a dark pigment.
Melanosis coli is not associated with an increased risk of colon cancer. However, melanosis coli may be associated with a higher incidence and number of colonic non-adenoma polyps and low-grade adenomas, suggesting that follow-up colonoscopy should be considered in patients with melanosis coli.
The relationship between long-term sennoside use and colorectal carcinogenesis remains contested. In one 2-year study, no intestinal lesions were induced in Sprague-Dawley rats by administration of a senna extract (35–42% sennosides) in drinking water. No ACF or tumors were observed in male Wistar rats after oral administration of senna extracts (30 or 60 mg/kg) 6 times per week for 110 weeks. Thus, it remains unconfirmed that long-term use of sennoside A in high doses induces intestinal hyperplasia and increases the risk of melanosis coli and subsequent colon cancer.
While sennosides are effective for short-term relief of constipation, their prolonged use is not recommended. Chronic use of sennosides can lead to electrolyte imbalances, dehydration, and dependence on laxatives. Hypokalemia from prolonged senna use can potentiate the effects of cardiac glycosides (e.g., digoxin), corticosteroids, thiazide diuretics, and loop diuretics, increasing the risk of cardiac arrhythmias.
Senna may reduce absorption of orally administered medications by accelerating intestinal transit time, and patients on warfarin or other narrow-therapeutic-index drugs should be monitored.
This is a well-documented and clinically significant safety concern specific to P. multiflorum-derived emodin dianthrones:
Dianthrone belongs to binuclear anthraquinone and has been studied as a potential hepatotoxic compound. The toxicity results of the four dianthrone compounds in human HepG2 cells at concentrations of 10 μM–40 μM for 48 hours showed that trans-emodin-physcion dianthrones and cis-emodin-physcion dianthrones showed significant hepatotoxicity.
Emodin, chrysophanol, emodin-8-O-β-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in P. multiflorum.
Trans-emodin dianthrones exhibited significant hepatotoxicity at the level of HepG2 cells, with a mechanism related to inhibiting the antioxidant system, causing mitochondrial dysfunction, and inducing apoptosis via JNK/Bax and PI3K/AKT/mTOR pathways.
An increasing number of reports have documented liver injury associated with P. multiflorum both domestically and internationally. A previous study found that dianthrones from P. multiflorum showed strong hepatotoxicity in the zebrafish model and may be potential toxicity markers.
The data show that four binuclear anthraquinone compounds were hepatotoxic and may be potential toxicity indicators for the safety evaluation of Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP), providing a theoretical basis for the improvement of PMRP quality standards.
Traditional processing methods for P. multiflorum are recognized to affect dianthrone content. The hepatotoxicity of Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata is of public concern; research has applied UHPLC-QQQ-MS/MS to determine six dianthrones in samples of raw and processed forms across nine cycles of steaming and sunning. These studies indicate that traditional processing reduces the dianthrone burden compared to raw material, though the safety implications have not been fully resolved in human trials.
Mutagenicity testing of sennosides has produced negative results in several bacterial and mammalian systems, except for a weak effect in Salmonella typhimurium strain TA102. No evidence of reproductive toxicity of sennosides has been found in rats and rabbits. Senna is not recommended during pregnancy due to potential weak genotoxic effects in animal studies.
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. Numerous published studies suggest that long-term use of sennoside A in large doses may have some adverse effects, including the occurrence of melanosis coli and carcinogenesis of colon cancer, thereby limiting its clinical use. As noted above, the colon cancer link remains unconfirmed by animal carcinogenicity studies.
Health conditions that Dianthrone may help support.
Body systems that Dianthrone may help support.
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