IngredientsAnthraquinone (systematic name: 9,10-anthracenedione; also written anthracene-9,10-dione) is the parent compound of one of the largest and most pharmacologically relevant classes of naturally occurring plant secondary metabolites. Its chemical structure is based on anthracene, formed by three fused aromatic rings containing two phenyl rings. The 9 and 10 positions carry two ketone (carbonyl) groups, which define the quinone oxidation state. In anthraquinones, positions 1, 4, 5, and 8 are referred to as α-positions, positions 2, 3, 6, and 7 as β-positions, and positions 9 and 10 as meso-positions; substituents include methyl, hydroxymethyl, carboxyl, aldehyde, hydroxyl, and methoxy groups.
Anthraquinones represent a group of naturally occurring quinones found generously across various plant species. The class encompasses a large number of structurally related derivatives, often grouped under the broader term hydroxyanthracene derivatives (HADs) or anthranoids. Anthraquinones are structurally divided into two classes, mononuclear and dinuclear. The most pharmacologically studied natural anthraquinones include emodin, aloe-emodin, rhein, chrysophanol, and physcion, all of which share the same fundamental scaffold. Emodin, aloe-emodin, rhein, chrysophanol, and physcion share the same 9,10-anthracenedione core but differ at a small number of positions by methyl, hydroxymethyl, carboxyl, hydroxyl, or methoxy groups.
Anthraquinones are the most abundant natural quinones. The class includes anthraquinone derivatives, their reduction products (oxyanthrone or anthrone), and derivatives of their dimers. These reduced forms are important in the context of laxative activity: if aglycones are present in dried herbs, they are always anthraquinones because anthrones are too unstable in the free state. Dianthrone glycosides such as the sennosides are not found in the living plant, being formed on harvesting and drying from monomeric anthrone glycosides.
Anthraquinones are widely distributed in various botanicals, such as rhubarb, aloe, and Fo-Ti, which are commonly clinically used in traditional Chinese medicines and dietary supplements. They are derived from plants from several families — including Ericaceae, Euphorbiaceae, Fabaceae, Liliaceae, Lythraceae, Polygonaceae, Rhamnaceae, Rubiaceae, Saxifragaceae, Scrophulariaceae, and Verbenaceae — as well as from some fungal and lichen species. Biologically active anthraquinone derivatives have also been identified in bacteria, fungi, and insects.
The principal plant sources used medicinally and as dietary supplements include:
Plant extracts containing anthraquinones are increasingly being used in cosmetics as well as in foods and pharmaceuticals. In the dietary supplement and botanical medicine context, anthraquinone-bearing plants are supplied in numerous forms:
The traditional therapeutic use of herbs containing anthraquinones was first initiated more than 4,000 years ago. Plants like rhubarb, senna, and cascara have been used for their laxative effects since prehistory.
The historical record demonstrates the use of anthraquinone-rich plants across numerous ancient cultures, predominantly as purgatives. Ancient Egyptian, Greek, and Roman medical texts document the use of these botanicals as remedies for digestive complaints, primarily constipation. Senna was used in ancient Egypt, while rhubarb has a documented history in traditional Chinese medicine stretching back thousands of years.
Rhubarb has been used to treat diseases since ancient times in China. Anthraquinone-containing single herbs combined with other drugs or single herbs (herb pairs) are a basic building block for Chinese medicine use. Rhubarb has been used in traditional medicine both as a laxative and antidiarrhoeal agent. Critically, rhubarb in small doses is used as an antidiarrhoeal, and in larger doses as a purgative — a pattern reflecting the dose-dependence of anthraquinone action. For example, a rhubarb-gardenia herb pair consisting of Rhei Radix et Rhizoma (Dahuang, containing anthraquinones) and Gardeniae Flos (Zhizihua, containing genipin) is used for treating cholestasis diseases.
Among herbs most commonly used in TCM for their anthraquinone content are Dahuang (Rhei Radix et Rhizoma), Heshouwu (Radix Polygoni Multiflori), Huzhang (Rhizoma Polygoni Cuspidati), Juemingzi (Semen Cassiae), Luhui (Aloe), and Qiancao (Rubiae Radix et Rhizoma).
In traditional Chinese medicine, anthraquinone-containing herbs are contraindicated in pregnancy because they promote a downward movement of energy. Cascara sagrada was widely used in European botanical medicine after its adoption from Native American practices, eventually becoming a widely prescribed pharmaceutical laxative in the 20th century. In Germany, rhubarb and senna have long had official status in herbal medicine.
Historically, anthraquinones have been used in herbal mixtures such as Essiac and Flor-Essence, which were popularized in the 1920s by Canadian nurse Rene Caisse, who claimed to have witnessed their efficacy in cancer treatment. The primary herbs in these botanical mixtures, rhubarb and sheep sorrel, are thought to contain anthraquinones. Such herbal extracts have been in use as a cancer treatment since the 1920s, when Caisse obtained the recipe from a woman who claimed it had cured her breast cancer. Caisse opened a clinic and treated patients for more than forty years. After her death, researchers at Memorial Sloan-Kettering in New York tested her product with inconclusive results.
The major naturally occurring anthraquinone derivatives studied for pharmacological activity are:
AQ laxatives include physcion, chrysophanol, aloe-emodin, rhein, and sennosides.
The laxative mechanism of anthraquinones has been studied extensively and involves multiple interconnected pathways. In anthraquinone glycosides, the β-glycosidic linkage is broken by β-glucosidases and reductases from intestinal bacteria, releasing the aglycones. Studies using dianthrone glycosides such as sennosides A and B suggest that most of these compounds pass through the upper GI tract without any change; however, they are subsequently metabolized in the colon by the natural flora (mainly bacteria) of the GI tract.
The mechanisms of action include 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; and secondly, there is an influence on secretion processes (change in absorption and secretion of water; retention of potassium, stimulation of active chloride secretion) resulting in enhanced fluid secretion.
A key molecular target has been identified: anthraquinone compounds rhein, aloe-emodin, and 1,8-dihydroxyanthraquinone stimulated iodide influx through the CFTR chloride channel in a dose-dependent manner. In short-circuit current assays, the three compounds enhanced Cl⁻ currents in CFTR-expressing cells, with EC50 values of 73±1.4, 56±1.7, and 50±0.5 μmol/L, respectively. In conclusion, natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulate colonic chloride and fluid secretion, and anthraquinone compounds potentiate CFTR function most probably through direct interaction with CFTR protein.
Anthraquinone-type laxatives also inhibit Na-K adenosine triphosphatase (ATPase) on enterocytes, which further inhibits the reabsorption of water, sodium, and potassium, ultimately excreting them into the feces.
After oral ingestion, anthraquinones are generally metabolized to active aglycones, which exert their laxative effect by damaging epithelial cells, leading directly and indirectly to changes in intestinal absorption, secretion, and motility.
Structure-activity considerations are important: in anthracene laxatives, hydroxylation of C-1 and C-8 is essential for activity. Glycosylation is also important, as the sugar moiety serves to transport the aglycone to the site of action in the large intestine. The dose-dependent nature of these effects is well established: their action is very much dose dependent. In lower doses, anthraquinones exert a milder tonic laxative effect; in larger doses, they will have a more powerful stimulant to cathartic effect.
Diacerein, an anthraquinone derivative, has in vitro and in vivo been shown to inhibit the production and activity of the cytokine interleukin-1β (IL-1β), which would otherwise prevent the production of cartilage-specific macromolecules. Diacerein decreases inflammatory cytokines and increases insulin secretion, enhancing insulin sensitivity and therefore improving glucose control.
These compounds exert antioxidant-related pharmacological actions including neuroprotective effects, anti-inflammation, anticancer, hepatoprotective effects, and anti-aging. Recently, there has been an upsurge in the development and utilization of anthraquinones as reactive oxygen species (ROS) regulators. Oxidative stress injury may be an important molecular mechanism responsible for potential hepatocytotoxicity and genotoxicity.
Emodin appears to enhance glucose tolerance and insulin sensitivity via activation of PPARγ and modulation of metabolic-related genes.
Aloe-emodin's anti-cancer effects have been reported to target critical signaling pathways like PI3K/Akt, MAPK, and NF-κB, which induce apoptosis and cell cycle arrest, regulate autophagy, and inhibit metastasis.
Anthraquinones are absorbed mainly in the intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow-rich organs and tissues such as blood, intestines, stomach, liver, lung, kidney, and fat.
A pharmacokinetic investigation of clinically used doses of senna-based laxatives in healthy volunteers ("Rhein and aloe-emodin kinetics from senna laxatives in man," Krumbiegel and Schulz, 1993) found that aloe-emodin itself was not detectable in plasma at any sampling point, whereas the related anthraquinone rhein reached peak concentrations of approximately 150–160 ng/mL with biphasic maxima at 3–5 hours and 10–11 hours after dosing, likely reflecting absorption of free rhein and rhein released from prodrugs by colonic bacterial metabolism.
Anthraquinones are absorbed mainly in the intestines, where free aglycones exhibit faster absorption than their glycosidic forms due to greater liposolubility; nonetheless, aloe-emodin generally displays low oral bioavailability and considerable inter-individual variability.
The aglycones are excreted in urine (causing the yellow or red-brown discolouration of urine) and bile as glucuronides and sulphates. The absorbed anthraquinones are metabolized in the liver, and anthraquinones and their metabolites are excreted in feces via biliary elimination and/or in urine.
In the case of senna, animal experiments with radio-labeled rhein-anthrone administered directly into the caecum demonstrated absorption of less than 10%.
Co-administration of different anthraquinones can alter each other's pharmacokinetics: emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lowers their plasma exposure levels.
This is the most clinically documented application of anthraquinone-containing botanicals. The laxative use of senna and other anthraquinone plants is well-established in human clinical use, supported by pharmacological studies, and recognized by regulatory bodies including the EMA and FDA.
Anthraquinone-rich herbs are most indicated for flaccid or atonic constipation that is characterized by a loss of bowel tone and infrequency of bowel movements. This is usually caused by a lack of exercise, prolonged bed rest, or habitual laxative use, and is more common in elderly populations.
Anthraquinones act directly on the intestinal mucosa, influencing several pharmacological targets, and their laxative effect is largely due to increased peristalsis of the colon, reducing transit time and consequently the reabsorption of water from the colon, making the stool more liquid and easing bowel movements.
Among senna fractions tested in a laxative potency study, the most potent laxative components (sennosides A+B) had the lowest acute toxicity, while fractions with very low laxative activity (such as rhein-8-glucoside) had the highest acute toxicity.
Evidence strength: The laxative efficacy of standardized senna and related anthraquinone preparations is among the best-documented uses in herbal medicine, supported by both mechanistic studies and clinical use data spanning decades. However, most controlled clinical trials are relatively short-term, and the strength of the specific RCT evidence base varies across individual anthraquinone sources.
Diacerein represents the best-studied anthraquinone derivative in formal clinical trials. A meta-analysis of randomized placebo-controlled trials assessed its symptomatic efficacy and safety in osteoarthritis. Diacerein has in vitro and in vivo been shown to inhibit the production and activity of IL-1β; this prevents the IL-1β effect of reducing production of cartilage-specific macromolecules. The meta-analysis was conducted by Bartels et al. at the Parker Institute, Frederiksberg Hospital, Denmark.
A randomized controlled trial protocol (DICKENS trial) was registered to recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis to assess diacerein versus placebo. Diacerein is a semisynthetic anthraquinone derivative that blocks IL-1β.
Evidence strength: Diacerein has been evaluated in multiple RCTs for osteoarthritis; the evidence indicates modest symptomatic benefit. It is approved as a pharmaceutical drug for osteoarthritis in several countries. The anti-inflammatory mechanism via IL-1β inhibition is well-characterized.
Emodin and diacerein have been shown to exert antidiabetic activities. A comprehensive review of anthraquinones in diabetes (Martorell et al., 2021, Evidence-Based Complementary and Alternative Medicine, PMC) searched multiple databases for evidence. Emodin appears to enhance glucose tolerance and insulin sensitivity via activation of PPARγ and modulation of metabolic-related genes, while diacerein decreases inflammatory cytokines and increases insulin secretion, enhancing insulin sensitivity and therefore improving glucose control.
Evidence strength: Evidence for antidiabetic effects of emodin is primarily preclinical (animal and in vitro). Diacerein, through its anti-inflammatory action, has some clinical evidence of metabolic benefit, but specific human trials for the antidiabetic effect of natural anthraquinones remain limited as of the available literature.
Aloe-emodin, chrysophanol, emodin, physcion, and rhein emerge as the most widely investigated naturally occurring anthraquinones, with robust in vitro evidence validating their antimicrobial efficacy against both drug-susceptible and resistant microbial pathogens relevant to modern clinical practice.
Rhein, physcion, aloe-emodin, and chrysophanol isolated from Rheum emodi rhizomes exhibited antifungal activity against Candida albicans, Cryptococcus neoformans, Trichophyton mentagrophytes, and Aspergillus fumigatus (MIC 25–250 μg/ml).
The antibacterial efficacy of a crude extract from Rheum rhabarbarum, along with its principal bioactive anthraquinones including aloe-emodin, rhein, emodin, chrysophanol, and physcion, was assessed against Aeromonas hydrophila, and the MIC-derived activity correlated positively with anthraquinone concentration.
Evidence strength: Antimicrobial activity is well-documented in vitro. Human clinical evidence for anthraquinones specifically as antimicrobial treatments is lacking; in vitro MIC values establish pharmacological plausibility but are insufficient to support clinical recommendations.
Some of the major chemical components of anthraquinone and its derivatives — such as aloe-emodin, danthron, emodin, chrysophanol, physcion, and rhein — have demonstrated potential anticancer properties. Aloe-emodin's anti-cancer effects include targeting critical signaling pathways like PI3K/Akt, MAPK, and NF-κB, inducing apoptosis and cell cycle arrest, regulating autophagy, and inhibiting metastasis. In addition to oncology, aloe-emodin exhibits potent anti-inflammatory, neuroprotective, and antiviral effects, primarily by reducing oxidative stress and regulating inflammatory responses.
Evidence strength: Cancer-related evidence for individual anthraquinones is predominantly preclinical (cell culture and animal models). After Rene Caisse's death, researchers at Memorial Sloan-Kettering in New York tested her anthraquinone-containing herbal product (Essiac) with inconclusive results. No high-quality human RCTs have established anthraquinone supplementation as an effective cancer treatment.
In current studies, rhubarb anthraquinone total aglycones have been reported to have neuroprotective functions and potential utility for the treatment of cerebral ischemic injury. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators compared with other groups administered individual anthraquinones, showing no significant difference from the nimodipine (positive control) group. The aloe-emodin + physcion group showed the most obvious anti-ischemic effect among groups administered two anthraquinones simultaneously. This study was conducted in a cerebral ischemia-reperfusion rat model.
Evidence strength: Neuroprotective evidence is exclusively preclinical (animal models). No human clinical trials have established anthraquinones as effective neuroprotective agents.
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects.
A study showed that Gardeniae Flos increased the Cmax and AUC of aloe-emodin, chrysophanol, emodin, and rhein in rats, indicating a synergistic effect of the rhubarb-gardenia herb pair on hepatoprotection.
Evidence strength: The anti-inflammatory and hepatoprotective evidence is largely based on animal and in vitro studies. Clinical human data is limited.
Dosages for anthraquinone-containing preparations vary substantially depending on the plant source, the specific preparation, and the therapeutic indication. The following dosages are those reported in the source literature:
The adverse effects of anthraquinone laxative drugs are more likely to result from the excessive loss of fluid and electrolytes, particularly potassium, associated with the use of high doses. Habituation occurs because chronic abuse raises aldosterone levels in response to electrolyte loss, diminishing their effectiveness. Higher doses also empty a larger portion of the colon, and the resulting natural absence of defecation over the next day leads to anthraquinone reuse.
Prolonged use and overdose can result in diarrhea, extreme loss of electrolytes (especially potassium), damage to the surface epithelium, and impairment of bowel function by damage to autonomic nerves. Increased stimulant laxative use and abuse can cause electrolyte derangements due to the rapid transit through the bowel and decreased absorption. In extreme cases, particularly with potassium imbalance and acute renal injury, the consequences may be fatal.
Melanosis coli is associated with the chronic use of laxatives, particularly those containing anthraquinones, such as senna, rhubarb, and cascara. It can develop within a few months of using anthraquinone-containing 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 dark pigment. Melanosis coli disappears with discontinuation of the drug.
Melanosis coli is not associated with an increased risk of colon cancer and is mainly associated with chronic laxative use, particularly anthraquinone-containing compounds. However, although there is no known association between melanosis coli and colorectal cancer, melanosis coli may be associated with a higher incidence of colonic non-adenoma polyps and low-grade adenomas; thus, follow-up colonoscopy should be considered in patients with melanosis coli.
Naturally occurring 1,8-dihydroxyanthraquinones are under consideration as possible carcinogens. The genotoxicity literature is complex and contains conflicting data: positive and negative results have been reported for anthraquinone in Salmonella mutation assays. Early studies reported that neither anthraquinone nor its metabolites were genotoxic in Salmonella mutagenicity assays. In later studies, anthraquinone was found to be mutagenic in the Salmonella mutagenicity assay in the absence of metabolic activation. It has been suggested that the carcinogenicity of anthraquinone might be due solely to the presence of 9-nitroanthracene, a contaminant at approximately 0.1% in the tested sample.
The International Agency for Research on Cancer (IARC) of the WHO classifies quinones as group 2B and group 3 carcinogens. IARC classifies 1-amino-2,4-dibromoanthraquinone, anthraquinone itself, dantron (chrysazin; 1,8-dihydroxyanthraquinone), 1-hydroxyanthraquinone, 2-methyl-1-nitroanthraquinone, and mitoxantrone as Group 2B carcinogens — that is, possibly carcinogenic to humans, but evidence of carcinogenicity in humans is limited.
The EFSA ANS Panel established that some hydroxyanthracene derivatives (HADs) "should be considered as genotoxic and carcinogenic unless there are specific data proving the contrary."
Importantly, tolerance and genotoxicity do not seem to be problems associated with senna specifically, especially when used periodically in therapeutic doses.
Safety concerns have been raised, including hepatotoxicity, nephrotoxicity, cardiotoxicity, carcinogenicity, and severe diarrhea. For example, emodin has caused hepatotoxicity in vitro and in rats, and may induce liver injury in humans. Among the 16 anthraquinones evaluated in a combined cytotoxicity/reverse dosimetry analysis, rhein was identified as a potential hepatotoxicant due to a combination of cytotoxicity, plasma concentration, and daily intake level.
In primary rat hepatocyte and HepG2 cell cytotoxicity experiments, the toxicity of chrysophanol was the lowest of the five rhubarb anthraquinones (rhein, emodin, aloe-emodin, physcion, and chrysophanol).
Contraindications for anthraquinone laxatives include ileus from any cause. Use in pregnancy and lactation is controversial. In traditional Chinese medicine, anthraquinone-containing herbs are contraindicated in pregnancy because they promote a downward movement of energy. A review article has reported that senna would appear to be the stimulant laxative of choice during pregnancy, probably because of the poor intestinal absorption of senna compared to other anthraquinone laxatives. Traditional use has shown that with careful use, senna may be used in the second and third trimester with minimal risk, but avoidance of use in the first trimester is recommended based on the potential for senna to be an abortifacient.
A systematic review and meta-analysis of 8 observational studies evaluated anthraquinone laxatives as a risk factor for colorectal cancer development. Eight observational studies were identified evaluating AQ laxatives as a risk factor for CRC development. The meta-analysis found that a history of AQ laxative use compared with other or no laxative use was associated with CRC development (OR: 1.41; 95% CI: 0.94–2.11), although not at a statistically significant level. The possible association persisted even after removal of outlier studies (OR: 1.51; 95% CI: 0.97–2.34). The authors concluded that the association did not reach statistical significance, and the observational study design cannot establish causation.
The compatibility of Chinese medicines is not the simple addition of therapeutic effects; on the contrary, ingredients promote reciprocal absorption and entrance to the lesion site, prolong residence time, increase blood drug concentration, change pharmacokinetic behavior, and synergistically enhance the drug therapeutic effect. This principle is practically relevant: co-administration of different anthraquinones can significantly alter systemic plasma exposures, as demonstrated in animal pharmacokinetic studies. Clinically, the most significant interaction concern from anthraquinone laxatives is the potentiation of hypokalemia when used together with cardiac glycosides (e.g., digoxin), antiarrhythmics, or corticosteroids — a mechanistic risk arising from anthraquinones' demonstrated inhibition of intestinal Na-K-ATPase and potassium loss.
At high doses, anthraquinone-rich herbs are gastrointestinal irritants, causing toxicity symptoms that can include nausea, vomiting, bloody diarrhea, dermatitis, dizziness, acute abdominal pain and cramping, and in severe cases, kidney damage.
Before 2002, products containing various components of Aloe vera (aloin, aloe-emodin, and barbaloin) were considered as oral over-the-counter (OTC) laxatives and regulated by the Food and Drug Administration (FDA). The FDA subsequently removed cascara sagrada and aloe laxative ingredients from the OTC market due to insufficient data to support their safety and efficacy under OTC laxative drug requirements, although these herbs remain available as dietary supplements.
Health conditions that Anthraquinone may help support.
Anthraquinones are the class of bioactive compounds found in senna, cascara, rhubarb, aloe, yellow dock, and buckthorn that provide the pharmacological basis for their colon-cleansing laxative effects. They stimulate colonic motility and inhibit water reabsorption. Recognized by the European Pharmacopoeia and multiple pharmacological references as the active principle of stimulant botanical laxatives.
Anthraquinone derivatives are the primary active constituents in multiple plant-based laxatives (senna, cascara, aloe, rhubarb, frangula). They stimulate colonic peristalsis and inhibit water/electrolyte reabsorption after colonic bacterial activation to anthrone metabolites. Pharmacopoeial standards for all major herbal laxatives specify anthraquinone or hydroxyanthracene derivative content as the key quality marker.
Body systems that Anthraquinone may help support.
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