Centaurium – Centaury (Centaurii herba)

Latin name of the genus:Centaurium
Latin name of herbal substance:Centaurii herba
Botanical name of plant:Centaurium erythraea rafn
English common name of herbal substance:Centaury

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Latin name of the genus: Centaurium
Latin name of herbal substance: Centaurii herba
Botanical name of plant: Centaurium erythraea Rafn
English common name of herbal substance: Centaury

Centaurium - Centaury - Centaurium erythraea Rafn

Table of Contents


MA: Marketing Authorisation;

TRAD: Traditional Use Registration;

Other TRAD: Other national Traditional systems of registration;

Other: If known, it should be specified or otherwise add ’Not Known’

1This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.

2Not mandatory field





II.1 I


II.1.1 Description of the herbal substance(s), herbal preparation(s) or combinations thereof

Herbal substance3:

Centaurii herba consists of the whole or fragmented dried flowering aerial parts of Centaurium erythraea Rafn s. l. including C. majus (H. et L.) Zeltner and C. suffruticosum (Griseb.) Ronn. (syn.: Erythraea centaurium Persoon; C. umbellatum Gilibert; C. minus Gars.) (Ph. Eur.).


: (Popov, 1969; BHP, 1979; Aquino et al., 1985; van der Sluis, 1985 ; Dombrowicz et al., 1988; Hellemont, 1988; Hänsel et al., 1992; Bisset, 1994; Schulz et al., 1998; Valentão et al., 2002; Bellavita, 2003; ESCOP, 2003)

Secoiridoid glucosides are the characteristic bittertasting constituents, principally (75%) swertiamarin and smaller amounts of gentiopicroside (gentiopicrin) and sweroside (bitterness value ca. 12,000) and centapricin (bitterness value ca. 4,000.000). Other iridoids include bitter m-hydroxybenzoyl esters of sweroside, and deacetylcentapicrin, centauroside (a dimeric secoiridoid), secologanin, 6’-m-hydroxy-benzoyl-loganin, dihydrocornin (a cyclopentane iridoid), gentioflavoside.

Analysis of different plant parts has shown a variety in the composition of the bitter ingredients. Due to the occurrence of the very bitter secoiridoid esters centapicrin and desacetylcentapicrin, fruits are more bitter than the flowers, leaves and stems. Swertiamarin is the major component in all parts of C. erythraea.

Secoiridoid alkaloids: gentianine and gentianidin;

Xanthones: 6 methoxylated xanthones, including eustomin (1-hydroxy-3,5,6,7,8-penta- methoxyxanthone) and 8-demethyl-eustomin and others;

Organic/Phenolic acids such sinapic, vanillic, syringic, oleanolic acid (0.1%);

as p-coumaric, o-hydroxyphenylacetic, ferulic, protocatechuic, hydroxyterephthalic and 2,5-dihydroxy-terephthalic acids and

Phytosterols: β-sitosterol, stigmasterol, campesterol and others;

Coumarins: 5-formyl-2,3-dihydroisocoumarin;

Miscellaneous: flavone components and anthocyanes.

Herbal preparations specified for the individual final product

A)Comminuted herbal substance for tea preparation

B)Powdered herbal substance

C)Liquid extract (1:1; ethanol 25% v/v)

D)Tincture (1:5; ethanol 70% v/v)

E)Soft extract (1:10; water)

3According to the ‘Procedure for the preparation of Community monographs for traditional herbal medicinal products’ (EMEA/HMPC/182320/2005 Rev.2) and the ‘Procedure for the preparation of Community monographs for herbal medicinal products with well-established medicinal use’ (EMEA/HMPC/182352/2005 Rev. 2).

Combination preparations with Centaurii herba

Madaus (1938), Weiss (1974) and Hellemont (1988) mention formulas containing Centaurii herba in combination with other herbal substances. At present authorised/registered combination products containing Centaurii herba are on the market in several EU Member States, amongst others: Czech Republic, Germany, United Kingdom, Austria, Poland, Spain and Estonia.

II.1.2 Information on period of medicinal use in the Community regarding the specified indication

Centaurium erythraea Rafn is used for many decades in the European Union mainly for the relief of digestive complaints (peptic discomfort) and lack of appetite. Centaurii herba was also used for the treatment of diabetes, snakebites, malaria, wounds and as an antipyretic, tonic and sedative. Preparations of this herb are described in different (old) Pharmacopoeias of European Member States4:

Centaurii herba (based on Erythraea centaurium Persoon) has been documented in DAB 6 (1936) and Ned. Pharm. III (1889) (van der Sluis, 1985).

Centaurii minoris herba is described in Pharmacopoeias of following member states: Austria, Czech Republic, Germany, Hungary, Poland, Romania and Spain (Martindale, 1977).

Erythraea centaurii herba florida is described: Ph. Ned. (1934), Belg. Pharm. IV (1940), (Hellemont, 1988).

Erythraea centaurii extractum fluidum is described in: Belg. Pharm. IV (1940) (Hellemont, 1988).

Extractum centaur. minor is described in: Belg. Pharm. IV (1940) (Hellemont, 1988).

Extractum centaurii (a soft extract) is described in the ‘Ergänzungsband zum deutschen Arzneibuch’ (EB 6, 1953) and (Hänsel et al., 1992; HagerRom, 2006).

Centaury – Centaurii herba is described in Eur. Ph. (Eur. Ph., 2008).

The medicinal use has also been documented in well-known handbooks dating from 1938 (Madaus), 1954 (Steinmetz), 1977 (Martindale), 1988 (Hellemont) and 1992 (Hänsel et al.) up to 2003 (ESCOP).

In ancient times Centaurii herba was used as a febrifuge in intermittent fever attacks, at dysmenorrhoea and as a sedative (Madaus, 1938; Hellemont, 1988).

According to Kneipp (1935) centaury has blood cleaning properties and is used for gastrointestinal complaints, Madaus (1938) claims it to be the best remedy against gastric juice burning sensation.

Steinmetz (1954) describes Erythraea centaurium (common names: small centaury or small knapweed) to be a bitter stomachic and febrifuge, to be used in chlorosis and jaundice; it also ‘purifies the blood, promotes the menses and improves the appetite’.

Bisset (1994) mentions its use as a bitter, for stimulating the appetite and increasing the secretion of the gastric juice, especially in chronic dyspeptic states and achylia. In folk medicine Centaurii herba was also employed as roborant and tonic.

4The various pharmacopoeias are not in agreement regarding the species of Centaurium. These discrepancies are due mainly to the confusion about the nomenclature and delimitation of C. erythraea s. l. and many synonyms are used in literature for C. erythraea Rafn (van der Sluis, 1985). Hybridisation occurs frequently causing morphological variability, resulting in taxonomic divergences. C. erythraea s. l. is an unresolved assemblage comprising diploid to hexaploid species related to C. erythraea subsp. erythraea (Mansion, 2005), see also II.1.1.

Centaury is used in dyspepsy and diarrhoea accompanied by liver and bile impairments or caused by an unbalanced diet and can be effective in flatulence (Hellemont, 1988).

According to Hänsel et al. (1992) Centaurii herba can be applied in dyspeptic and stomach disorders, and in lack of or for stimulation of appetite.

Newall (1994) mentions the traditional use of the infusion in anorexia.

In Germany extracts of Centaurii herba are components in registered gastrointestinal, cholagogue and urological remedies (Bisset, 1994; Walther, 2004).

For an overview on the documented applications of Centaurii herba , see II.3.2.

II.2.1 Pharmacology

II.2.1.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof

Documentation regarding the route of administration

Oral administration is the main route of administration for Centaurii herba preparations.

Centaurii herba has also been used topically in the treatment of inflammations, wounds (Hänsel et al., 1992), snakebites and eczema (Dweck, 1997).

Results from an animal study demonstrated a significant anti-inflammatory activity after application of an aqueous extract of centaury in the air pouch granula test (Berkan et al., 1991; Hänsel et al., 1992).

However, in the handbooks detailed information on composition of the preparation, posology, duration of use and clinical data is lacking. Therefore, topical use as a traditional herbal medicinal product does not fulfil the requirements of Directive 2004/24/EC.

Phytochemical research data on major components in

Centaurium erythraea

Xanthones and the secoiridoids sweroside, swertiamarin and gentiopicrin have been identified in several Centaurium species. On the basis of chemical derivation, the authors concluded sweroside to be probably identical with the compound known as ‘kantaurin’ (van der Sluis, Labadie, 1981).

An HPLC method was developed and used for the determination of gentiopicrin (gentiopicroside) in Centaurium erythraea (Kaluzova et al., 1995).

Piatczak et al. (2006) demonstrated that the level of secoiridoids is modified by both transformation by Agrobacterium rhizogenes and by the development stage of transformed plants. The total content of the compounds (expressed as the sum of gentiopicroside, sweroside and swertiamarin) in transformed plants was 280 mg/g dry weight and was 8 times the content in the sample of commercially available C. erythraea herb.

In the course of a phytochemical study of C. erythraea, six methoxylated xanthones (1,5-hydroxy-3-methoxyxanthone, 1-hydroxy-3,5,6-trimethoxyxanthone, 1-hydroxy-3,5,6,7- tetramethoxyxanthone, 1-hydroxy-3,5,6,7,8-pentamethoxyxanthone, 1-hydroxy-3,7,8- trimethoxyxanthone and 1,8-dihydroxy-3,5,6,7-tetramethoxyxanthone) were isolated and identified by spectroscopic means. Subsequently a detection method was developed for the determination of these and other methoxylated xanthones occurring in the chloroform extract of small centaury aerial parts. The methodology developed was applied to twelve samples, and in all of them, nine xanthones were identified and quantified (Valentão et al., 2002).

– Kumarasamy et al. (2003) isolated the two secoiridoid glycosides, swertiamarin and sweroside from the aerial parts of Centaurium erythraea.


Although the mechanism of action is still unclear, it is assumed that the bitter constituents stimulate the gustatory nerves in the mouth and give rise to an increase in the secretion of gastric juice and bile, thereby enhancing the appetite and digestion (Evans, 1996).

Pharmacological activities of whole extracts of centaury herb

Increase in sputum (Hänsel et al., 1992) and gastric juice secretion (Blumenthal et al., 1998; Hänsel et al., 1992).

Antipyretic activity of a dry aqueous extract of centaury was observed in rats after administration of 50-100 mg/animal by gavage in a yeast-induced fever test (Berkan,1991; Hänsel et al., 1992; Newall, 1994). The antipyretic properties are assumed to be due to the phenolic acid. No fever-lowering/antipyretic effects were observed after pretreatment with centaury (Newall, 1994).

Anti-inflammatory activity of a dry aqueous extract of centaury was observed in Freund’s adjuvant-induced polyarthritis in rats treated orally with 10-500 mg per day (Berkan, 1991). Inhibition of carrageenan-induced paw oedema by 40% has been found after oral intake of 100 mg/kg body weight of a dry ethanolic extract of centaury (Capasso et al., 1983; Hänsel et al., 1992; Newall, 1994).

A diuretic effect was observed in rats after oral administration of 8% or 16% aqueous extract of centaury at 10 ml/kg body weight daily for one week, with the most effective dose for water and electrolyte excretion being 8%. From the fifth day of treatment urine volume increased significantly with the lower dose and both doses led to a significant increase of sodium, chloride and potassium excretion. At the end of the treatment a diminution in creatine clearance was observed (Haloui, 2000).

A hepato-protective activity of a methanol extract of the leaves of C. erythraea was evaluated against acetaminophen-induced liver toxicity in rats. An oral dose of 300 mg/kg/day for 6 days or a single dose of 900 mg/kg for 1 day exhibited a significant protective effect by lowering serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH). The hepato-protective activity was also observed by histopathological examination of liver sections (Mroueh et al., 2004).

Antioxidant activity of small centaury infusion has been reported (Valentão, 2001; Valentão, 2003).

An aqueous extract of C. erythraea did not show analgesic properties (Berkan, 1991).

Pharmacological activities of combination preparations

– A concentration-dependant relaxant effect was observed in rats fed on spontaneous ileum contractions and on rat ileum pre-contracted with carbachol, after administration of an hydroethanolic extract of four herbs, including Erythraea centaurium (L.) Borkh. (Botion et al., 2005).

Pharmacological activities of isolated compounds in centaury herb

Antimalarial properties of gentiopicrin have been mentioned in handbooks (Newall, 1994).

Antibacterial activity could be observed for swertiamarin and sweroside; both compounds inhibited the growth of Bacillus cereus, Bacillus subtilis, Citrobacter freundii and Escherichia

coli. While swertiamarin was also active against Proteus mirabilis and Serratia marcescens, sweroside inhibited the growth of Staphylococcus epidermidis (Kumarasamy et al., 2002).

Isolated swertiamarin showed anticholinergic activity, significantly inhibiting carbachol- induced contractions of the proximal colon in rats in a dose-dependant manner after oral administration at 150 mg/kg and 300 mg/kg body weight (Yamahara et al., 1991).

Isolated gentianine, administered to rats at 100 mg/kg body weight, showed besides anti- ulcerogenic activity in the water immersion stress test an inhibitory action against gastric secretion (Yamahara et al., 1978).

A depressive effect on the central nervous system is reported for mice treated orally with 30 mg/kg body weight gentianine. An inhibition of spontaneous movement activity and an increase of hexo-barbital induced sleeping time were observed (Yamahara et al., 1978).

Two methoxylated xanthone derivatives, eustomin and demethyleustomin, isolated from the aerial parts of Centaurium erythraea Rafn showed antimutagenic properties in Salmonella typhimurium strains TA98, TA100, and TA102. The antimutagenic character of the compounds was supported by the effects shown in post-treatment experiments as well as by results obtained with recA mutants of E. coli and Bacillus subtilis. Isolated eustomin at 50 μg/plate showed strong inhibition, 76% against 2-NF and 64% against 2-AA in strain TA-100; 8-demethyleustomin was also active, with results of 43% and 39% respectively, but no inhibition was detected from secoiridoid or polar fractions of centaury (Schimmer, Mauthner, 1996).

II.2.1.2 Assessor’s overall conclusions on pharmacology

The traditional use of Centaurium erythraea Rafn, herba, as a (powdered) herbal drug, herbal tea or hydroalcoholic extract, for the relief of mild dyspeptic/gastrointestinal disorders/complaints and lack of appetite is well documented in a number of handbooks.

Results from in vitro and in vivo studies with extracts, and isolated constituents, support the traditional use as appetite and digestion stimulant.

Experimental data to support the antipyretic activity are very limited. In addition, no specific posology for this indication could be found. Therefore, the use as an antipyretic cannot be recommended.

II.2.2 Pharmacokinetics

II.2.2.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof

No data available.

II.2.2.2 Assessor’s overall conclusions on pharmacokinetics

No data available, no conclusion can be drawn.

II.2.3 Toxicology

II.2.3.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof

– No published data could be found on the toxicity of extracts of centaury. However one case report has been found, reporting a possible relation between the acute and cytolytic hepatitis and the intake of the herbal preparation Copaltra (containing Coutarea latiflora 50 mg and Centaurium erythraea 50 mg). As it concerned a combination product, no conclusions on the safety of Centaurium can be drawn (Wurtz et al., 2002).

– General toxicity of gentiopicroside, swertiamarin and sweroside was determined in the brine shrimp lethality bioassay. LD50 values measured for swertiamarin and sweroside were 8.0 microg/ml and 34 microg/ml, respectively. Podophyllotoxin, which was used as the positive control showed an LD50 of 2.8 microg/ml (Kumarasamy et al., 2003a; Kumarasamy et al., 2003b).

II.2.3.2 Assessor’s overall conclusions on toxicology

Toxicological data on centaury are very limited. Experimental data are only available for isolated compounds. Nonetheless, neither the chemical composition nor the long-term widespread use in the European Community suggest that there is a (potential) risk associated with the use of centaury extract. Yet, due to the lack of data on acute and chronic toxicity, repeated dose toxicity, genotoxicity, mutagenicity, carcinogenicity, reproductive and developmental toxicity, a list entry for Centaurii herba cannot be recommended.

II.3.1 Clinical Pharmacology

No data available.

II.3.1.1 Pharmacodynamics

No data available.

II.3.1.2 Pharmacokinetics

No data available.

II.3.2 Clinical Efficacy / Longstanding use and experience

For centaury herb the following medicinal uses have been reported in European handbooks:

* (Chronic) digestive/dyspeptic/gastro-intestinal problems: achylia, gastric juice burning, stomach, obstipation, anorexia, lack of appetite/appetite stimulation, chlorosis, jaundice, functional disturbances in the bile system etc.

II.3.2.1 Posology

There are no dose response studies available. The following posology is described in the literature:

A) Comminuted herbal substance for tea preparation (1:20)

5 1 teaspoon = ca. 1.8 g (Bisset, 1994)

C) Liquid extract (1:1; alcohol 25% v/v)

6 30 drops = ca. 1.5 g

Duration of use

No information could be found on the duration of use. As clinical safety studies are lacking, it is recommended to limit the duration of use to 2 weeks.

II.3.2.2 Clinical studies (case studies and clinical trials)

No published data available7.

II.3.2.3 Clinical studies in special populations (e.g. elderly and children)

No published data available.

II.3.2.4 Assessor’s overall conclusions on (clinical) efficacy / the traditional medicinal use

The available clinical data do not support well-established use.

The traditional use of Centaurium erythraea Rafn, herba, as a (powdered) herbal drug, herbal tea or hydroalcoholic extract, for the relief of mild dyspeptic/gastrointestinal disorders/complaints and lack of appetite is well documented in a number of handbooks. The traditional use is supported by pharmacological data.

II.3.3 Clinical Safety/Pharmacovigilance

II.3.3.1 Patient exposure

No data available.

II.3.3.2 Adverse events

None known (Newall, 1994; Blumenthal et al., 1998; Walther, 2004).

II.3.3.3 Serious adverse events and deaths

No data available.

II.3.3.4 Laboratory findings

No data available.

II.3.3.5 Safety in special populations and situations

II. Intrinsic (including elderly and children) /extrinsic factors

No data available.

II. Drug interactions

7 The electronic databases of PubMed, Embase and International Pharmaceutical Abstracts were searched with the search terms ‘Centaurium erythraea’ combined with ‘human’, ‘clinical trial’ , ‘randomised controlled trial’ and ‘review’.

None known (Blumenthal et al., 1998).

II. Use in pregnancy and lactation

No data available. In accordance with general medical practice, the product should not be used during pregnancy or lactation.

II. Overdose

No toxic effects have been documented. After intake of high dosages, stomach disturbances and nausea have been reported (Hellemont, 1988).

This information has not been included into the monograph because the dosage is not given in the reference.

II. Drug abuse

No data available.

II. Withdrawal and rebound

No data available.

II. Effects on ability to drive or operate machinery or impairment of mental ability

No studies on the effect on the ability to drive and use machines have been performed.

II. Contra-indications

Due to the reflexively stimulation of gastric juice secretion caused by bitter ingredients, products containing Centaurii herba must not be used in case of active peptic ulcer disease (Bisset 1994; Walther, 2004).

II.3.3.6 Assessor’s overall conclusions on clinical safety

Clinical safety data are lacking. However, up to now no (serious) side effects have been reported. Furthermore, the chemical composition of centaury herb does not give reasons for safety concerns.

As there is no information on reproductive and developmental toxicity, the use during pregnancy and lactation cannot be recommended.

Data on use in children or adolescents are not available.

The use of Centaurium erythraea Rafn has a long tradition in Europe, mainly in mild dyspeptic/gastrointestinal disorders and in temporary loss of appetite. The medicinal use has been documented continuously in well-known handbooks. Therefore, Centaurii herba fulfils the requirements of Directive 2004/24 EC for classification as a traditional herbal medicinal product. Its use in above-mentioned disorders is considered plausible on the basis of bibliographic and pharmacological data.

The pharmacological activity is attributed to the whole extract; however emphasis is put on the group of secoiridoid glycosides (‘bitters’) with main components swertiamarin, gentiopicroside, centapicrin and sweroside. Also xanthones, phenolic acids and other ingredients may contribute to the pharmacological activity of Centaurii herba.

Centaurii herba is used in the following pharmaceutical forms and posology:

A)Comminuted herbal substance for tea preparation: single dose: 1-4 g, up to 4 times daily;

B)Powdered herbal substance: single dose 0.25-2 g, up to 3 times daily;

C)Liquid extract (1:1; ethanol 25% v/v): single dose: 2-4 ml, up to 3 times daily;

D)Tincture (1:5; ethanol 70% v/v): single dose: 1.5-5 g, up to 3 times daily;

E)Soft extract (1:10; water): single dose: 0.2 g; daily dose: 1-2 g.

Toxicological data on centaury is very limited. Experimental data is only available for isolated compounds. Nonetheless, neither the chemical composition nor the long-term widespread use in the European Community suggests that there is a (potential) risk associated with the use of centaury extract. Yet, due to the lack of data on acute and chronic toxicity, repeated dose toxicity, genotoxicity, mutagenicity, carcinogenicity, reproductive and developmental toxicity, a list entry for Centaurii herba cannot be recommended.

There are no clinical safety data for extracts of Centaurii herba. In the documentation of the traditional medicinal use within the Community, no serious adverse effects have been reported.

Due to lack of data, Centaurii herba preparations cannot be recommended for children and adolescents below the age of 18 years, in pregnancy and lactation and must not be used in case of active peptic ulcer disease. During the public consultation, an interested party requested to include a posology for adolescents. This was not endorsed because the claim was not supported with experimental safety and/or exposure data.