IngredientsRubiaceae is a family of flowering plants variously called the madder family, bedstraw family, or coffee family. The family takes its name from the Madder genus Rubia. Rubiaceae is a large family of 630 genera and about 13,000 species found worldwide, especially in tropical and warm regions. More recent taxonomic compilations are slightly higher: the 611 genera and over 13,100 species that make up the vast family Rubiaceae are primarily found in tropical and warm climates. According to Delprete et al., the Rubiaceae family is one of the largest angiosperm families with a large number of species distributed throughout the world, including deserts and high mountains.
From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this, and large amounts of both iridoids and indole alkaloids are produced.
Rubiaceae is not a single ingredient but a vast plant family. In dietary supplement and traditional medicine contexts, it is best understood as an umbrella grouping of medicinally significant genera and species, each with its own phytochemical profile and uses. The most studied medicinal and supplement-relevant species include:
Species like Adina cordifolia, Anthocephalus cadamba, Cinchona officinalis, Coffea arabica, Morinda citrifolia, and Paederia foetida have received considerable research attention on the Indian subcontinent.
Rubiaceae is one of the largest families of angiosperms and consists of approximately 600 genera and more than 10,000 species. It is essentially a tropical, woody family widely distributed in Brazil's main ecosystems: Amazon, Cerrado, and Atlantic Forest. Morinda citrifolia is native to Southeast Asia, widely distributed west to India and Sri Lanka, east to Polynesia, south to northern Australia, and north to Jiangsu, China. It is also distributed in the Caribbean, Mexico, and South America. Uncaria tomentosa is a tropical medicinal vine originating in the Amazon rainforest and other areas of South and Central America.
The root and rhizome of Rubia cordifolia (called Qiancao in China and Indian madder in India) is a well-known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, and swelling and pain caused by injuries from falls. Ayurvedic preparations traditionally use the rhizome and roots—sometimes dried into powders or extracted into tinctures.
Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, have exhibited anti-inflammatory and/or immunomodulatory activities. Noni (M. citrifolia) is consumed in the form of juice, capsules, tablets, and powders made from the fruit, leaves, or roots. Gardeniae Fructus (GF), the desiccated mature fruit of Gardenia jasminoides, belongs to the Rubiaceae family and has abundant medicinal value; it is usually used in combination with other drugs to treat diseases such as fever and jaundice in damp heat syndrome in TCM clinical practice.
The use of Rubia cordifolia dates back thousands of years, particularly within Ayurvedic and Traditional Chinese Medicine (TCM) systems. In Ayurveda, it is one of the chief "rakta shodhana" (blood purifiers) and is categorized under "varna prasadaka" herbs — agents that enhance complexion and skin tone. Ancient Ayurvedic texts like the Charaka Samhita and Sushruta Samhita describe its application in treating chronic skin diseases, ulcers, jaundice, and gynecological imbalances. It was also used topically to heal wounds and bruises, given its capacity to dissolve stagnant blood and improve microcirculation.
This drug is used to treat rheumatism, menstrual pain, urinary system diseases, dropsy, paralysis, amenorrhea, and jaundice in India. In Ayurveda, R. cordifolia has been used as a coloring agent for medicinal oils, and applied externally to inflamed areas, ulcers, and fractures.
Manjistha (Garance) is described as a bitter and astringent Ayurvedic herb that pacifies Kapha and Pitta dosha. It has been used traditionally for centuries due to its effectiveness in cleaning and purifying the blood and circulatory system.
Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant widely distributed in China and India. As a medicinal plant, it was first recorded in a formula with endoconch of Sepiella maindroni in "Huangdi Neijing," the most important ancient book in TCM. Rubiae Radix et Rhizoma (RRR), the dried root and rhizome of R. cordifolia, is a famous TCM used for thousands of years. With its excellent activity to cool blood, eliminate stasis, stop bleeding, and unblock meridians, it has been considered in "Bencao Gangmu" and other ancient medical books as an important herbal drug for curing syndromes caused by blood heat. Thus, RRR is still listed in the Chinese Pharmacopoeia.
The plant water decoction can be taken orally to treat diarrhea, and can also be used externally as a foot bath when children are too young to take it. R. cordifolia is also a main ingredient of the formula named "Er-Xie-Ting granule," which is used to treat acute infantile diarrhea in China.
Gardeniae Fructus has medicinal value described as "purging fire and eliminating annoyance, clearing heat and diuresis, cooling blood, and detoxifying," usually used in combination with other drugs to treat fever and jaundice in damp heat syndrome in TCM clinical practice.
Rubia cordifolia is known as btsod in Traditional Tibetan Medicine, where it is used to treat blood disorders; spread heat, excess heat in the lungs, kidneys, and intestines; and reduce swelling. It is a component of the "three reds" (dmar gsum), a subcompound included in many Tibetan preparations to remove excess heat in the blood.
Uncaria tomentosa is a Rubiaceae used for at least 2,000 years among some Peruvian tribes, especially the Asháninka. Commonly known as cat's claw, it has been traditionally used to treat asthma, abscesses, fever, urinary tract infections, viral infections, and wounds, and has been found to be effective as an immune system rejuvenator, antioxidant, antimicrobial, and anti-inflammatory agent.
More than 50 new substances have been isolated from alkaloid-rich Uncaria species. Uncaria tomentosa, known as "unha de gato" (cat's claw), is one of the most used plants in Brazilian folk medicine.
More than 60 Rubiaceae species are used in Sub-Saharan Africa for more than 70 medicinal indications, including malaria, hepatitis, eczema, oedema, cough, hypertension, and diabetes. In medicine, trees of the genus Cinchona (Rubiaceae) are of great interest because of their alkaloids, the most familiar being quinine, the first effective agent in treating malaria. In this last topic the Rubiaceae family received great attention by scientists.
Morinda citrifolia L., commonly known as noni, is a small evergreen tree native to Southeast Asia and Australia. It is now widely cultivated across tropical and subtropical regions, including the Pacific Islands, Puerto Rico, the Dominican Republic, and Brazil, particularly in the Central-West and Northeast regions. This species has attracted considerable attention due to its extensive use in traditional medicine, as well as its potential therapeutic and industrial applications. In Hawaii, M. citrifolia is called Noni, whereas in India it is called Indian mulberry. Malaysians call it mengkudu and in Southeast Asia it is called nhaut, while in the Caribbean it is called the painkiller bush or cheese fruit.
In the Cinchonoideae subfamily, Cinchona species are the source of quinine, isolated in 1820 by Pelletier and Caventou, and which for about 200 years was the only active substance against malaria, and can be considered as responsible for the development of synthetic antimalarials.
The genus Uncaria (Rubiaceae) comprises 34 species, many of which are usually used as traditional Chinese medicines (TCMs) to treat hypertension, fever, headache, gastrointestinal illness, and fungal infection.
Iridoids, anthraquinones, triterpenes, and indole alkaloids as well as other varying alkaloid subclasses have been shown to be the most common secondary metabolites in Rubiaceae. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza, and Morinda. Many studies detect flavonoids, iridoids, triterpenes, phytosterols, anthraquinones, and others in Rubiaceae plants.
Phytochemical studies on Brazilian Rubiaceae, especially those from Cerrado and Atlantic Forest, have shown the presence of a number of antifungal secondary metabolites, mainly triterpenes, iridoids, and caffeic ester derivatives. In addition, indole and oxindole alkaloids, coumarins, and flavonoids have also been isolated.
So far, more than 100 structurally diverse compounds have been identified from the Rubiaceae family, mainly including alkaloids, glycosides, flavonoids, triterpenoids, phenols, and volatile compounds.
Studies have found that R. cordifolia is rich in more than 100 compounds, mainly including anthraquinones, naphthoquinones, anthraquinone glycosides, naphthoquinone glycosides, bicyclic hexapeptides, triterpenoids, and polysaccharides.
Four hydroxyanthraquinones — pseudopurpurin, purpurin, munjistin, and xanthopurpurin — naturally occurring in Rubia spp. and varying by the substituents at positions 1, 2, and 3 were thoroughly investigated to reveal the relevance of their structural features for interactions with enzymes.
Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first described in 1981 and has been reported for many biological activities. Rubiadin has sparked a lot of interest in recent years due to its excellent pharmacological effects including anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral activities.
The Rubia genus contains anthraquinones (AQs), particularly alizarin and purpurin, which have pharmacological effects that are anti-inflammatory, antioxidant, anticancer, hemostatic, and antibacterial. The coloring matter of the roots is a mixture of purpurin and munjistine; the roots also contain small amounts of xanthopurpurin, pseudopurpurin, munjistine, alizarin, and its glucosides.
The alkaloids of Rubiaceae are indole alkaloids. They may occur in tetracyclic or pentacyclic rings. U. tomentosa is rich in many phytoconstituents such as oxindole and indole alkaloids, glycosides, organic acids, proanthocyanidins, sterols, and triterpenes.
Research on Uncaria has focused on alkaloids in phytochemistry and pharmacology over the past 15 years, including biosynthesis, phytochemistry, and structural chemistry. Particularly, the pharmacological activities surrounding the central nervous system and cardiovascular system of representative compounds rhynchophylline and isorhynchophylline are described in detail.
The occurrence and distribution of iridoids, alkaloids, and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies of Rubiaceae. Iridoids are particularly concentrated in the Rubioideae and Cinchonoideae subfamilies and are associated with the anti-inflammatory, antimicrobial, and antidiabetic activities reported for many genera including Morinda, Hedyotis, and Galium.
The Rubiaceae family has significant economic importance. For instance, species in the Ixoroideae subfamily are rich in caffeine, a compound that acts as a stimulant for the central nervous system, as well as a diuretic, bronchodilator, and antimigraine agent.
Stability studies of compound RA-V, a cyclic hexapeptide from R. cordifolia, in simulated intestinal and gastric fluids showed that the anticancer activity remained unchanged before and after treatment, indicating that RA-V was stable. As a result, it could be bioavailable when orally used in therapeutics and possibly a drug candidate for cancer treatment.
Meta-analysis of preclinical studies on Uncaria tomentosa demonstrated that extracts decreased the cytokines interleukin (IL)-6 (SMD: −0.72, 95% CI: −1.15, −0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: −1.19, 95% CI: −1.89, −0.48, p = 0.001).
Purpurin, a compound from Rubia cordifolia, reduces inflammation and modulates immune responses, showing protective effects against joint damage in rheumatoid arthritis models. It lowers pro-inflammatory cytokines and inhibits MMP3. Its hydroxyl-substituted anthraquinone nucleus confers strong antioxidant capacity, metal-chelating activity, and the ability to intercalate with DNA and interact with key enzymes, thereby underpinning its multifaceted pharmacological actions.
Isolated anthraquinones from R. cordifolia were evaluated for their inhibitory effects on NO production in LPS-activated RAW264.7 macrophage cells. Compounds 1, 3, and 10 exhibited significant inhibitory activities with IC50 values of 14.05, 23.48, and 29.23 μmol·L⁻¹, respectively.
The Rubiaceae family is of interest for preventing and treating metabolic syndrome due to its rich content of metabolites renowned for their antioxidative, anti-inflammatory, and metabolic regulatory properties. These compounds influence transcription factors and mitigate chronic low-grade inflammation, liver lipotoxicity, oxidative stress, and insulin resistance.
The anti-peroxidative property of the solvent-free alcoholic extract of R. cordifolia was studied in rat liver homogenate. It prevents cumene hydroperoxide-induced malondialdehyde formation in a dose- and time-dependent manner. This effect is accompanied by maintenance of reduced glutathione level even in the presence of the above toxin.
Pseudopurpurin and munjistin were found to be more structurally similar to the reference fluoroquinolones (S)-gatifloxacin and (S)-levofloxacin than their non-carboxylated analogues. Docking poses of pseudopurpurin and munjistin in the active sites of the protein-DNA complexes of DNA gyrase and DNA topoisomerase IV revealed their plausible molecular modes of action against Gram-positive and Gram-negative bacteria.
Compounds in Rubiaceae species influence transcription factors and mitigate chronic low-grade inflammation, liver lipotoxicity, oxidative stress, and insulin resistance. Reviews have collected data validating the traditional uses of the Rubiaceae family for treating metabolic syndrome and associated non-communicable diseases from experimental models and human subjects, highlighting the mechanisms through which their extracts and metabolites modulate glucose and lipid metabolism at molecular, biochemical, and physiological levels.
Bioactive components from Rubiaceae plants are considered responsible for various bioactivities including anti-oxidation, anti-inflammation, immunomodulation, antitumor effects, effects on the coagulation-fibrinolysis system, neuroprotection, and other effects.
(Rubiaceae) Uncaria tomentosa is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. Scientific evaluation of this use has advanced considerably. A systematic review and meta-analysis was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. Studies published before July 26, 2023, identified in PubMed, Embase, and Scopus, were analyzed by four independent reviewers. Preclinical studies confirmed the anti-inflammatory and/or immunomodulatory effects and the low toxicity of U. tomentosa extracts.
Meta-analyses showed that the extracts significantly decreased IL-6 (SMD: −0.72, p = 0.001) and NF-κB (SMD: −1.19, p = 0.001). However, the extracts did not significantly alter IL-1, IL-10, or TNF-α levels. Overall, the studies were at high risk of bias because most did not report sample size calculations, the number of excluded animals, or possible conflicts of interest. The main limitation is the small number of studies included in the meta-analysis.
Clinical trials (joint disease): A randomized, double-blind, placebo-controlled trial (Mur et al., 2002, Journal of Rheumatology) followed 40 patients with active rheumatoid arthritis over 24 weeks. Those receiving a freeze-dried U. tomentosa extract showed statistically significant reductions in painful and swollen joint counts compared to placebo. Effect sizes were described as modest, but the safety profile was excellent and the results were consistent.
A prospective Phase II clinical study was registered to assess the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day on individuals with advanced solid tumors, with no further therapeutic options and at least 2 months of life expectancy. Results of this study were not yet available in the reviewed sources.
Evidence characterization: The anti-inflammatory evidence base for U. tomentosa includes mechanistic data (NF-κB inhibition) and limited but positive human trials, particularly for inflammatory joint disease. The overall human trial evidence remains small, and study quality is variable. Preclinical data are supportive but predominantly animal-model based.
In medicine, trees of the genus Cinchona are of great interest because of their alkaloids, the most familiar being quinine, the first effective agent in treating malaria. In the Cinchonoideae subfamily, Cinchona species are the source of quinine, isolated in 1820 by Pelletier and Caventou, and which for about 200 years was the only active substance against malaria, and can be considered as responsible for the development of synthetic antimalarials.
Through biological screening following leads supplied by traditional healers, many Rubiaceae plants exhibited antimalarial, antimicrobial, antihypertension, antidiabetic, antioxidant, and anti-inflammatory activities. Bioactive compounds including indole alkaloids, terpenoids, and anthraquinones have been isolated from these bioguided fractionation studies.
Evidence characterization: The use of quinine from Cinchona as a clinically validated antimalarial is historically established and pharmacologically well-documented. Other Rubiaceae species used ethnobotanically for malaria in Africa (e.g., Nauclea latifolia, Morinda lucida) have supporting in vitro and animal data, but lack large-scale controlled human trials.
The Rubiaceae family is promising for preventing and treating metabolic syndrome and associated non-communicable diseases due to its rich content of metabolites renowned for their antioxidative, anti-inflammatory, and metabolic regulatory properties. Species from the Rubiaceae family are some of the most extensively studied, with hundreds of reports in the scientific literature concerning their diverse pharmacological effects and, remarkably, their therapeutical activities related to metabolic syndrome, such as hypoglycemic, antihypertensive, and hypolipidemic effects.
Evidence characterization: Evidence for anti-metabolic syndrome effects from Rubiaceae plants is predominantly preclinical (in vitro and animal models). Some human clinical data exist for specific species (e.g., M. citrifolia), but are derived from small and sometimes poorly controlled trials. The current body of evidence is considered preliminary.
Morinda citrifolia L. (Rubiaceae), commonly known as noni, is widely used as a complementary and alternative therapy in many countries due to its numerous beneficial effects on health. Studies in animal models revealed its activity as anti-dyslipidemia, anti-lipogenesis, antifungal, hepatoprotective, hypotensive, immunostimulatory, anti-alopecia, photoprotective, antitumor, antiviral, anticancer, antidopaminergic, and antimicrobial.
Its traditional uses are increasingly supported by experimental evidence, particularly for conditions such as inflammation, oxidative stress modulation, and bacterial infections. However, future research and clinical trials are still essential to continue to validate these applications and to develop safe and standardized dosing protocols.
Evidence characterization: The clinical trial evidence for noni is growing but still limited. Most studies involve small sample sizes, heterogeneous preparations, and short durations. Animal and in vitro data are extensive and supportive but cannot substitute for robust human trials.
Rubia cordifolia Linn. (Rubiaceae) was studied for anti-inflammatory effects in rats with carrageenan paw edema. The plant showed significant anti-inflammatory activity at doses of 10 and 20 ml/kg of water extract. The activity was comparable to that of phenylbutazone (100 mg/kg). This represents animal model evidence; controlled human clinical trials for R. cordifolia's anti-inflammatory effects are not yet established in the reviewed sources.
Uncaria tomentosa (UT) is a medicinal plant popularly known as cat's claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. In vitro antiviral activity of the UT bark hydroalcoholic extract against the Brazilian chikungunya virus (CHIKV) strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results demonstrated that UT inhibits CHIKV infection in a dose-dependent manner.
Evidence characterization: Antiviral data for cat's claw and related Rubiaceae species are predominantly in vitro. No substantial human clinical trial data for antiviral outcomes are available in the reviewed sources.
Cyclic hexapeptides and anthraquinones from Rubia cordifolia have been studied for their mechanisms in preferential inhibition of cancer signaling pathways and the possible crosstalk effect with other previously reported signaling pathways. In several in vitro and in vivo tests, the main chemicals alizarin and purpurin, isolated from Rubia species, have shown diverse pharmacological activity, including antigenotoxic, anticancer, neuromodulatory, and antimicrobial effects.
Evidence characterization: Cancer-related evidence for Rubiaceae compounds is at an early stage — predominantly in vitro and animal studies. No clinical trial data establishing efficacy for cancer treatment from Rubiaceae-derived supplements were identified in the reviewed sources.
Research on Uncaria genus over the past 15 years has focused on neuroprotective effects of alkaloids represented by rhynchophylline and isorhynchophylline. Plants in the Rubiaceae family are widely used in traditional medicine for their diverse therapeutic effects, including antioxidant, antiviral, antibacterial, and anti-inflammatory properties. Additionally, these plants exhibit activity against cardiovascular and central nervous system diseases.
Evidence characterization: Neuroprotective and cardiovascular evidence for Rubiaceae alkaloids (particularly from Uncaria species) is primarily based on preclinical in vitro and animal studies. Robust human clinical evidence is currently lacking.
The following dosages are reported specifically as used or studied; they are not recommendations and vary by species, extract type, and indication:
No standardized, universally established clinical dosage for Rubiaceae family preparations as dietary supplements has been confirmed in large-scale human clinical trials. Dosages in the reviewed literature vary widely by species and preparation method.
Lucidin, a constituent of Rubia tinctorum, is genotoxic in vitro and in vivo. Data on carcinogenic activity of this compound were not available, but it has been shown that madder root (Rubia tinctorum) — which contains lucidin — causes tumours in liver and kidneys of rats.
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.
The mutagenicity or carcinogenic potential of the active anthraquinones is a matter of concern. At present, there is a lack of research and literature on the in vivo metabolism and the metabolites of these components, so in terms of safe medication, the Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) of these naturally occurring anthraquinones should be the urgent concern.
Noni juice is made from the fruit of the Morinda citrifolia L. plant. It was authorized in the European Union in 2003 for use as a novel food ingredient in pasteurized fruit drinks under the Novel Foods Regulation, after its safety was assessed by the EU's Scientific Committee on Food (SCF).
Following information from the Austrian authorities, the European Commission asked EFSA to re-assess the safety of noni juice by reviewing recent case reports of severe hepatitis in people consuming noni juice. The Panel confirmed the findings of the SCF regarding the studies on toxicity as well as genotoxicity and allergenicity. From a toxicological point of view, noni juice has been adequately tested.
In a formal genotoxicity assessment of noni fruit substances, none of the noni fruit test substances showed genotoxic signs up to 5,000 and 2,000 μg/plate in the Ames and micronucleus tests, respectively. In the chromosomal aberration test, neither the fruit puree nor aqueous extract showed structural and numerical aberrations up to 5,000 and 4,650 μg/mL, respectively, irrespective of metabolic activation.
Reports of acute hepatitis linked to noni preparations have been documented in the clinical literature (cited by EFSA review), and isolated case reports of hepatotoxicity remain a concern, particularly at high doses or in individuals with pre-existing liver conditions.
When animals such as cattle, sheep, and goats eat certain plants from the genus Palicourea (Rubiaceae), it can be deadly. These plants cause serious illness and sudden death in livestock, with "erva-de-rato" (Palicourea marcgravii) being particularly dangerous. The main culprit behind these toxic effects is a chemical called sodium monofluoroacetate, which is found naturally in these plants and is highly poisonous to animals. Palicourea species are not used as dietary supplements, but their presence in the Rubiaceae family illustrates that not all members are safe for consumption.
Several herbal products and constituents with a long history of folk usage are suspected carcinogenic and/or hepatotoxic. Herbal products have also been shown to inhibit and/or induce drug-metabolizing enzymes. Species-specific interaction data for individual Rubiaceae members used as supplements are not yet well-characterized in large clinical interaction studies.
Preclinical studies confirmed the anti-inflammatory and/or immunomodulatory effects and the low toxicity of U. tomentosa extracts. Extracts of the stems, stem barks, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity.
R. tinctorum L. is recorded in the 14th edition of the modern Russian Pharmacopoeia with a diuretic effect. However, given its genotoxic and carcinogenic potential noted by the European Commission, it is not considered safe for general dietary supplement use within the EU framework.
Health conditions that Rubiaceae may help support.
Body systems that Rubiaceae may help support.
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