IngredientsThe medicinal part of Rubia tinctorum is the dried root. The genus name Rubia derives from the Latin ruber, meaning "red." Common names include madder, dyer's madder, and Turkish madder. The term "madder" refers to two principal species of flowering plants in the family Rubiaceae: Rubia tinctorum, known as dyer's madder or Turkish madder, and Rubia cordifolia, known as Indian madder. Both species belong to the same family as coffee and gardenias.
The perennial plant grows to a height of 60 to 100 cm. The pencil-thick rhizome creeps widely underground. The stem is quadrangular with backward-turning prickles at the edges. The stems are at times so thin that they are more descendent than erect. The leaves are in whorls, in fours below, in sixes above, and are oblong to lanceolate with one rib and protrudingly reticulate beneath. The plant is indigenous to southern Europe, western Asia, and North Africa, and is cultivated elsewhere.
In a monograph in the Pharmacopoeia of the USSR, Rhizomata et radices Rubiae is described as the rhizome and roots of Rubia tinctorum L. (syn. R. iberica (Fish. ex DC) K. Koch). R. tinctorum L. is also recorded in the 14th edition of the modern Russian Pharmacopoeia with a diuretic effect.
Traditional madder extract is produced through water or alcohol extraction of the Rubia tinctorum root, a process that preserves the full spectrum of compounds. Its pigments are present as glycosides and aglycones, up to 2–3.5% of dry weight. The color shades of madder vary from scarlet, carmine red, and pink (high content of pseudopurpurin and/or purpurin, called pink madder or rose madder) to red with a bluish tint (alizarin lakes). Preparations historically encountered in trade and medicine include dried and powdered root, aqueous decoctions, hydroalcoholic tinctures, and standardized dry extracts. It has been used since ancient times as a vegetable red dye for leather, wool, cotton, and silk. For dye production, the roots are harvested in the first year. The outer brown layer gives the common variety of the dye, and the lower yellow layer the refined variety. The dye is fixed to the cloth with help of a mordant, most commonly alum.
The dye properties of the madder root appear to have been known from the earliest historical times; cloth dyed with madder has been found on ancient Egyptian mummies, and madder was used for dyeing the cloaks of Libyan women in the time of Herodotus (5th century BCE). Archaeologists have found traces of madder in linen in Tutankhamen's tomb (1350 BC) and in the ruins of Pompeii.
It is the erythrodanon of Pedanius Dioscorides, who wrote of its cultivation in Caria, and of Hippocrates, and the Rubia of Pliny. Madder was employed medicinally in ancient civilizations and in the Middle Ages. In his Natural History, Pliny described it as a diuretic and as capable of treating jaundice and lichen planus. The Encyclopedia of Medicinal Plants (Chevallier, 2001) also notes its use in the ancient world as a diuretic and as a medicine to treat jaundice, sciatica, and paralysis.
Madder was also employed as a medicinal treatment for amenorrhea (failure to menstruate) in ancient and medieval times.
During medieval Europe, madder cultivation boomed — Dutch growers became famous for "root of dyers," and the plant fueled the textile industry until synthetic dyes emerged in the 19th century. Herbalists like Nicholas Culpeper (1653) still recommended madder tea or tincture for urinary issues and gout. Dr. Meyrick of Birmingham wrote in his Family Herbal (1790) that it "cures the jaundice and is useful in the beginning of dropsies [oedema]."
From the mid-17th to the 19th century, the uniform of many British soldiers included a red coat dyed with madder — hence the nickname 'Redcoats' for soldiers.
Madder root was highly valued in various ancient healing systems, including Ayurveda, Unani, and traditional European medicine. In India, references to "Manjishtha" — a close relative sometimes interchanged with R. tinctorum in classical Ayurvedic texts like the Charaka Samhita (circa 1st–2nd century CE) — highlight its use in blood purification rituals. Though true Rubia tinctorum appears to have been introduced to the subcontinent later via trade routes, it gradually earned a reputation for supporting liver and skin health, similar to Manjishtha (Rubia cordifolia).
In traditional Persian medicine — Unani — the root was used to cool 'excess heat' in the body, calm inflamed tissues, and as a mild diuretic. In Morocco, R. tinctorum L. has been used to treat renal disease, cardiac disease, hypertension, and diarrhoea.
Thousands of patients in European countries were treated chronically in the past, against kidney stones, with madder root preparations (R. tinctorum) at high doses. Its listing in the former USSR Pharmacopoeia specifically for a diuretic effect underscores its longstanding official medicinal status in that region.
In 1869, the German chemists Graebe and Liebermann synthesised artificial alizarin, which was produced industrially from 1871 onwards, effectively ending the large-scale cultivation of madder. In the 20th century, madder was only grown in some areas of France.
A number of compounds have been characterized from the roots of R. tinctorum (the source of commercial madder colour) by various analytical methods. Among these compounds are alizarin, ruberythric acid, purpurin, lucidin, rubiadin, mollugin, 1-hydroxy-2-methylanthraquinone, tectoquinone (2-methylanthraquinone), nordamnacanthal, 1-hydroxy-2-methoxyanthraquinone, 1,3-dihydroxy-2-ethoxymethylanthraquinone, scopoletin (7-hydroxy-6-methoxycoumarin) and the glucosides and/or the primeverosides of these compounds.
So far, some 36 anthraquinones have been detected in R. tinctorum by various workers. The main components are di- and tri-hydroxy-anthraquinones, alizarin and purpurin and their derivatives, ruberythric acid (alizarin-primeveroside), pseudopurpurin, and lucidinprimeveroside. Rubiadin, munjisti, quinizarin (1,4 dihydroxyanthraquinone), lucidin, nordamnacanthal, xanthopurpurin, and 1,8-dihydroxyanthraquinone are also identified from plant tissues.
The majority of the anthraquinones present in the plant itself or in plant extracts are glycosides. The color-producing principles of madder root are chiefly alizarin (C₁₄H₈O₄) and purpurin (C₁₅H₈O₅), which exist in the root partly free, but mostly combined with sugar in the form of more or less easily decomposable glucosides.
The most important dye pigment in madder root is alizarin, its pigment code is Pigment Red 83 with colour index number CI 75,330. From a chemical point of view, alizarin is a hydroxyl derivative of anthraquinone (i.e., 1,2-dihydroxyanthraquinone). The most interesting of the colouring substances is alizarin, now termed dihydroxyanthraquinone. This occurs as orange-red crystals, almost insoluble in water, but readily soluble in alcohol, ether, the fixed oils, and alkaline solutions. Alizarin and purpurin were first isolated by the French chemist Pierre Jean Robiquet in 1826.
Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is predominantly isolated from Rubia species such as Rubia cordifolia and Rubia tinctorum, and has long been used as a natural dye due to its intense red coloration. Purpurin (1,2,4-trihydroxyanthraquinone) is one of several hydroxy derivatives of anthraquinone evaluated for antioxidative and anti-inflammatory activities. The number and location of the OH groups seems to be largely responsible for the observed large variations in the trends of antioxidative properties.
1,3-Dihydroxy-2-hydroxymethylanthraquinone (lucidin) occurs in R. tinctorum in the form of glycoside conjugates. Lucidin is of particular toxicological significance (see Section 6 on Safety).
Additional constituents of madder root include sugar (10 to 15 per cent), pectin, albuminous bodies, yellow xanthine of Kuhlmann (1824), and rubichloric acid. The extract is also rich in polysaccharides and flavonoids that contribute to its pharmacological activity.
The mechanism of the antioxidative effect involves abstraction by the antioxidant of a high-energy reactive free electron from free radicals. The electron is then dissipated (delocalized) within the phenolic OH groups and the aromatic ring of the antioxidant to a less reactive, lower-energy free radical. In comparative in vitro testing, purpurin showed the strongest antioxidant and good enzyme inhibitory effects among related anthraquinones.
Purpurin suppressed atopic dermatitis-associated inflammation (TNF-α/IFN-γ-induced) in HaCaT cells via inhibition of the activation of protein kinase B (AKT), mitogen-activated protein kinase (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Purpurin showed a significantly anti-inflammatory effect by reducing the content of IL-6, TNF-α, and IL-1β and increasing IL-10 in macrophage models.
The mechanism of anticancer action of anthraquinones includes, among others, inhibition of proliferation, invasion, migration, and metastasis, and induction of apoptosis of cancer cells. Alizarin also inhibits the genotoxicity of mutagens such as heterocyclic amines and PAHs, which is related to its ability to inhibit CYP activity (CYP1A1, CYP1A2, and CYP1B1) responsible for the activation of mutagens. It can also be considered as an osteotropic candidate in bone cancer due to its strong antiproliferative effect on osteosarcoma cells, inhibition of ERK phosphorylation, and arrest of the cell cycle in the S phase. It also has an affinity for calcium, thus achieving high target specificity for bone tissue.
Structure–activity relationship analyses highlight the critical role of hydroxyl substitutions in modulating antioxidant, anticancer, antibacterial, and neuroprotective properties through radical stabilization, DNA intercalation, and metal chelation.
Alizarin, contained in madder, stains newly-formed bone but not cartilage, a property traceable to its chemical affinity for calcium. Gottlieb, in 1914, expressed the belief that alizarin has a specific chemical affinity for calcium. This calcium-binding capacity is the physicochemical basis for both the traditional use in urolithiasis (where the intent was to bind to calcium-based stones) and alizarin's enduring utility as a bone stain in biological research.
Madder dye inhibits stone formation, exhibits a diuretic effect, and has bactericidal properties. Antimicrobial activity of madder was assessed using a low-diffusion method, and it was found that aqueous and alcoholic extracts of the plant are effective against some Gram-positive and Gram-negative bacteria, yeast, filamentous fungi, and actinomycetes.
Traditional basis: Extracts from R. tinctorum are used for the treatment of kidney and bladder stones. This is perhaps the best-documented traditional application and the one that attracted the most modern scientific scrutiny.
Preclinical evidence: A local survey in Morocco revealed the frequent use of Rubia tinctorum L. for the treatment of kidney stones. One study explored whether RT ethanolic and ethyl acetate extracts could prevent urolithiasis in an experimental 0.75% ethylene glycol and 2% ammonium chloride-induced rat model, and also determined the potential antioxidant potency and polyphenol composition of these extracts. An EG/AC regimen for 10 days induced the formation of bipyramid-shaped calcium oxalate crystals in the urine. Simultaneous oral administration of the madder dye extract prevented the development of kidney stone disease in rats.
The use of madder dye is reported as effective for treating calcium phosphate (vitlocite, apatite, hydroxyapatite, carbonatapatite) and struvite urolithiasis in preclinical contexts.
Evidence strength: To the knowledge of the authors of the 2021 Moroccan study, no experimental study had previously reported an anti-urolithiasic effect of RT in formal models. The available evidence is therefore preclinical (animal models) only, with no published controlled human clinical trials identified in peer-reviewed databases. The evidence base is preliminary.
In vitro and preclinical evidence: The anthraquinones of Rubia species, particularly alizarin and purpurin, have pharmacological effects that are anti-inflammatory, antioxidant, anticancer, hemostatic, and antibacterial. In one preclinical study, the effect of purpurin on inflammation was investigated using macrophage RAW264.7 inflammatory cells induced by lipopolysaccharide (LPS), and adjuvant-induced arthritis (AIA) rat models. Purpurin showed significantly anti-inflammatory effect by reducing the content of IL-6, TNF-α, and IL-1β and increasing IL-10. It also improved joint injury and regulated immune markers, and reduced MMP3 content in AIA rats.
Evidence strength: Evidence is exclusively from in vitro cell assays and animal models. No human clinical trials on the anti-inflammatory effect of Rubia tinctorum preparations were identified. This area of research is preliminary.
Alizarin and purpurin are di- and trihydroxyanthraquinones derived from Rubia tinctorum L. Previous pharmacological studies have demonstrated that they exhibit a certain degree of selective inhibitory effects towards cancer cells, suggesting their application as targeted drugs for cancer. Research aimed to investigate the suitability of hydroxyanthraquinones of Rubia tinctorum L. for targeted tumor therapy.
From a counterintuitive perspective, the presence of purpurin in bacterial mutagenicity assays was found responsible for a marked inhibition of mutagenicity induced by food-derived heterocyclic amines. In another study, four anthraquinone pigments, including alizarin and purpurin, showed significant antigenotoxic activities on DNA damage induced by carcinogens in Drosophila.
Evidence strength: All anticancer evidence is from in vitro and preclinical models. No human clinical oncology trials have been conducted. This field is highly preliminary, and the same constituents that show selective anticancer activity in some models also raise genotoxic safety concerns in others (see Section 6).
Beyond its traditional use as a natural dye, purpurin has recently gained attention for its multifaceted pharmacological activities, particularly in neuroprotection. Evidence from preclinical studies indicates that purpurin exerts beneficial effects in Alzheimer's disease, depression, ischemic stroke, and age-related cognitive decline, primarily through anti-tau aggregation, cholinesterase inhibition, serotonergic modulation, antioxidant activity, and anti-inflammatory mechanisms.
Evidence strength: Evidence for neuroprotective effects is preclinical (in vitro and animal model) only. No human trials have been reported.
In one published study investigating cytotoxic, antioxidative, and enzyme inhibition effects, cytotoxic effects were evaluated with cell inhibition rate by MTT assay. Different chemical assays were used to evaluate antioxidant properties. Enzyme inhibitory activities were analyzed against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase. Results: these components showed antioxidant and enzyme inhibition activity.
Evidence strength: This evidence is in vitro only. Clinical translation has not been demonstrated.
The experimental period of bone growth study between 1722 and 1847 consisted in the study of bone growth by the drilling of benchmark holes into the diaphysis, and examination of growing bones in madder-fed animals. It was caused by alizarin, contained in madder and staining the newly-formed bone, but not the cartilage. Duhamel, in 1739, introduced the coloring of growing bone with madder in ossification studies. Alizarin was recognized as the principal staining ingredient of the plant in 1826, by Robiquet and Colin. Vital staining with alizarin compounds has been used to study the nature of the growth of bone for more than two centuries.
This application is scientific rather than therapeutic: madder's role was as a research tool enabling foundational discoveries in skeletal biology, rather than being used to treat bone disorders in patients.
Based on the converging evidence from traditional use records and modern preclinical research, madder root is associated with the following body systems:
No well-powered human clinical dosage studies exist for madder root. The following dosages appear in the primary literature and pharmacopoeial or toxicological records:
No standardized or consensus human dosing range for madder root as a dietary supplement has been established by any regulatory or pharmacopoeial body, and its therapeutic use is no longer permitted in Germany (see Section 8).
The genotoxic activity of lucidin (1,3-dihydroxy-2-hydroxymethyl-9,10-anthraquinone), a natural component of Rubia tinctorum L., was tested in a battery of short-term tests. The compound was mutagenic in five Salmonella typhimurium strains without metabolic activation, but the mutagenicity was increased after addition of rat liver S9 mix. In V79 cells, lucidin was mutagenic at the hypoxanthine-guanine phosphoribosyl transferase gene locus and active at inducing DNA single-strand breaks and DNA-protein cross-links as assayed by the alkaline elution method. Lucidin also induced DNA repair synthesis in primary rat hepatocytes and transformed C3H/M2-mouse fibroblasts in culture.
Lucidin primeveroside is hydrolysed in rats to the aglycones 1,3-dihydroxy-2-hydroxymethylanthraquinone (lucidin) and rubiadin, which are excreted in urine. Lucidin is mutagenic in bacteria, mutagenic and genotoxic in cultured mammalian cells, and forms DNA adducts in mice.
The uptake of the anthraquinone glycosides alizarinprimeveroside and lucidinprimeveroside leads to the rodent carcinogen 1-HA, and to the highly genotoxic compounds lucidin and rubiadin. This extends prior studies and supports the suggestion that the therapeutic use of Rubia tinctorum may involve a carcinogenic risk.
To elucidate the possible carcinogenicity of madder root, three groups of male and female ACI rats received either a normal diet or a diet supplemented with 1 or 10% drug for a total period of 780 days. Weight gain and morbidity were not different among the three groups. Non-neoplastic lesions related to the treatment were evident in the liver and kidneys of both sexes. Moreover, dose-dependent increases in benign and malignant tumour formation were observed in the liver and kidneys of treated animals.
Lucidin is genotoxic in vitro and in vivo. Data on carcinogenic activity of this compound were not available per se, but it has been shown that madder root — which contains lucidin — causes tumours in liver and kidneys of rats. The DNA-adduct pattern from colon, liver, and kidneys of rats showed one adduct that was also found when deoxyguanosine-3′-monophosphate was incubated with lucidin in vitro. This supports the assumption that lucidin is involved in the carcinogenic effects of Rubia tinctorum.
Root extracts have shown genotoxic effects in several test systems, which are attributed to the presence of the anthraquinone derivative lucidin. One of the other main components, alizarin primeveroside, is transformed into 1-hydroxyanthraquinone when given orally to the rat, in which this metabolite has carcinogenic activity.
The use of herbal medicines prepared from the root of Rubia tinctorum (madder) is no longer permitted in Germany. Root extracts have shown genotoxic effects in several test systems, which are attributed to the presence of the anthraquinone derivative lucidin.
Due to the genotoxic activity and oncogenic potential of R. tinctorum L., the Commission of the European Communities has considered R. tinctorum L. as a plant with serious risks.
Madder color was long accepted for use as a food additive in Japan and South Korea, but not in the United States of America (USA) and the European Union (EU). It was present among food additives that were already marketed or used on the date of the amendment of the Japanese Food Sanitation Law in 1995 and then appeared in the List of Existing Food Additives.
Lucidinethylether, which is formed from lucidin by extraction of madder roots with boiling ethanol, was also mutagenic in Salmonella, but only after addition of rat liver S9 mix. This is of particular relevance to ethanolic preparations of madder root, as the extraction process itself can generate an additional genotoxic compound.
Alizarin stains the bones of animals that feed upon madder plants, and that property was used by 19th-century physiologists. By extension, significant ingestion of madder root preparations can cause temporary reddening of urine, an effect documented anecdotally in historical sources and consistent with the pigment's physicochemical properties.
Since herbal medicines are often used in conjunction with conventional drugs, kinetic and clinical interactions are a cause for concern. A demonstration of the safety of herbal medicines for registration purposes should include at least in vitro and in vivo genotoxicity assays, long-term rodent carcinogenicity tests (for drugs intended to be continuously used for more than 3 months or intermittently for more than 6 months), reproductive and developmental toxicity studies, and investigation of the effects on drug-metabolizing enzymes. Madder root has not satisfied these requirements in contemporary regulatory frameworks.
The safety evidence for madder root is among the most robust aspects of its scientific record — and it points toward significant risk with internal use of whole-root preparations. The genotoxicity of lucidin is supported by multiple independent assay systems, and the animal carcinogenicity data (hepatocellular adenomas and renal cortex adenocarcinomas) are derived from controlled long-term rodent studies. Some studies have reported that rubiadin exerted strong genotoxicity as well as played a critical role as an initiator of carcinogenesis. These findings collectively underpin the regulatory prohibitions in Germany and the European Union.
Health conditions that Madder may help support.
Body systems that Madder may help support.
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