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|
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
- I.REGULATORY STATUS OVERVIEW1
- II.ASSESSMENT REPORT
- BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC
- AS AMENDED
- (TRADITIONAL USE)
- II.1 I
- II.1.1 Description of the herbal substance(s), herbal preparation(s) or combinations thereof
- Herbal substance3:
- Herbal preparations specified for the individual final product
- Combination preparations with Centaurii herba
- II.1.2 Information on period of medicinal use in the Community regarding the specified indication
- 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
- Phytochemical research data on major components in Centaurium erythraea
- Pharmacological activities of whole extracts of centaury herb
- Pharmacological activities of combination preparations
- Pharmacological activities of isolated compounds in centaury herb
- II.2.1.2 Assessor’s overall conclusions on pharmacology
- II.2.2 Pharmacokinetics
- II.2.2.1 Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- II.2.2.2 Assessor’s overall conclusions on pharmacokinetics
- II.2.3 Toxicology
- II.2.3.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- II.2.3.2 Assessor’s overall conclusions on toxicology
- II.3.1 Clinical Pharmacology
- II.3.1.1 Pharmacodynamics
- II.3.1.2 Pharmacokinetics
- II.3.2 Clinical Efficacy / Longstanding use and experience
- II.3.2.1 Posology
- Duration of use
- II.3.2.2 Clinical studies (case studies and clinical trials)
- II.3.2.3 Clinical studies in special populations (e.g. elderly and children)
- II.3.2.4 Assessor’s overall conclusions on (clinical) efficacy / the traditional medicinal use
- II.3.3 Clinical Safety/Pharmacovigilance
- II.3.3.1 Patient exposure
- II.3.3.2 Adverse events
- II.3.3.3 Serious adverse events and deaths
- II.3.3.4 Laboratory findings
- II.3.3.5 Safety in special populations and situations
- II.184.108.40.206 Intrinsic (including elderly and children) /extrinsic factors
- II.220.127.116.11 Drug interactions
- II.18.104.22.168 Use in pregnancy and lactation
- II.22.214.171.124 Overdose
- II.126.96.36.199 Drug abuse
- II.188.8.131.52 Withdrawal and rebound
- II.184.108.40.206 Effects on ability to drive or operate machinery or impairment of mental ability
- II.220.127.116.11 Contra-indications
- II.3.3.6 Assessor’s overall conclusions on clinical safety
I.REGULATORY STATUS OVERVIEW1
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
BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC
II.1.1 Description of the herbal substance(s), herbal preparation(s) or combinations thereof
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.).
Constituents: (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
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
Organic/Phenolic acids such sinapic, vanillic, syringic, oleanolic acid (0.1%);
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
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
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.2.1.1 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
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
–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
– 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
–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).
–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
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
–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
–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
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.2.2.1 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.2.3.1 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
II.3.1 Clinical Pharmacology
No data available.
No data available.
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:
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
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.18.104.22.168 Intrinsic (including elderly and children) /extrinsic factors
No data available.
II.22.214.171.124 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.126.96.36.199 Use in pregnancy and lactation
No data available. In accordance with general medical practice, the product should not be used during pregnancy or lactation.
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.188.8.131.52 Drug abuse
No data available.
II.184.108.40.206 Withdrawal and rebound
No data available.
II.220.127.116.11 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.
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
–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:
B)Powdered herbal substance: single dose
C)Liquid extract (1:1; ethanol 25% v/v): single dose:
D)Tincture (1:5; ethanol 70% v/v): single dose:
E)Soft extract (1:10; water): single dose: 0.2 g; daily dose:
–Toxicological data on centaury is very limited. Experimental data is only available for isolated compounds. Nonetheless, neither the chemical composition nor the
–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.