Sisymbrium – Hedge mustard (Sisymbrii officinalis herba)
| Latin name of the genus: | Sisymbrium |
| Latin name of herbal substance: | Sisymbrii officinalis herba |
| Botanical name of plant: | Sisymbrium officinale (l.) scop. |
| English common name of herbal substance: | Hedge mustard |
Used to: Mouth and throat disorders;
Latin name of the genus: Sisymbrium
Latin name of herbal substance: Sisymbrii officinalis herba
Botanical name of plant: Sisymbrium officinale (L.) Scop.
English common name of herbal substance: Hedge mustard
1. Introduction
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Herbal substance(s)
Dried flowering aerial parts of Sisymbrium officinale (L.) Scop. (= Erysimum officinale L.) contain a minimum of 0.3% of total glucosinolates expressed as sinigrin (C10H16KNO9S2; Mr397,5) (calculated for the dried herbal substance) (Ph. Fr. 1998).
According to the Hagers Handbuch (Hänsel et al. 1994) in traditional medicine, mainly the fresh flowering plants of Sisymbrium officinale (hedge mustard) are used. The dried herb is used only in special cases.
Main active compounds
Dried flowering aerial parts contain: total glucosinolates 0.63 and 0.94%, mucilages 13.5 and 10.9%, total sugar alcohols 8.9 and 10.2%, total flavonoids 0.50 and 0.56%, respectively (Carnat et al. 1998).
Sulphated compounds
The chemical markers of Sisymbrium officinale are sulphated compounds, particularly glucosinolates, isothiocyanates and sulphated lactones, are also found in mustard oil (Gruenwald et al. 2004). According to the Hagers Handbuch, in the fresh plant mainly sinigrin (an allylglucosinolate) and gluconapin
Apart from glucoputranjivin an isopropyl isothiocyanate was also isolated from an aqueous dry extract (4:1) of dry aerial parts of Sisymbrium officinale. The chemical analysis of this extract revealed the absence of sinigrin and presence of putranjivine, the glucosinolate marker of Sisymbrium officinale (in a concentration of 0.5 mg/g) and proline (Di Sotto et al. 2010 and 2012).
Figure 1: Molecular structure and biosynthesis of putrajivine (Di Sotto et al. 2010.)
Isothiocyanates were the main hydrolytic products of glucosinolates isolated from fresh plant material (58.3% vs. 0.5% nitriles) and from fresh plant material after autolysis (32.5% vs. 1.4% nitriles). The nitrile content of dried plant material isolate was significantly higher (24.4%), although isothiocyanates were still the main degradation products (33.7%) (Blazević et al. 2010).
The fresh herb contains thiocyanic acid (Kern et al. 1979).
Cardiac steroid glucosides (cardenolide glycosides)
Latowski et al. 1979 has attempted a chemotaxonomical classification of 12 species of three genera Cruciferae (Erysium, Cheirantus and Sisymbrium) containing cardenolide glycosides. The raw material was the flowering tops of shoots (10 cm), collected in Pharmacognostical Garden of Medical Academy in Poznań. The raw material was extracted with ethanol, then treated with ethyl acetate (debalasted) and the cardenolide fraction was extracted with chloroform. The dry residue was analysed for cardenolides. Determination of cardenolides was performed according to the method Soos and Baumgarten (1963). Measurement of extinction at 500 nm after chromatographic separation (Rf 0.43) was carried according to Kowalewski method. The content of cardenolides in Sisymbrium officinale (L.) Scop was 49.8 mg%, considering Baljet reagent and 42.2 mg% as sum of
Table 1. (Latowski et al. 1979)
The analysis of monoglycosides, and particularly of helveticoside and corchoroside, permitted the isolation of 5 groups which suggest change in the systemic rank of some taxons.
Table 2. (Larowski et al. 1979)
Rapporteur’s comment:
The tables above show that Sisymbrium officinale has a special composition considering the rate of the two main cardenolide monoglycosides.
The chemical structure of cardenolide glycosides found in Sisymbrium officinale is very similar to the structure of strophantin K (see Figure 2) which was used in the form of i.v. preparation as a heart tonic in the
Figure 2. The chemical structure of cardenolide glycosides
| corchoroside A | helveticoside |
strophanthin K
Volatile compounds
Blazevits et al. (2010) investigated the volatile compounds of hedge mustard (leaves and flowers) (Sisymbrium officinale) isolated from fresh (with or upon autolysis) and from the dried plant material.
Other compounds
The
Herbal preparation(s)
Flos: Comminuted herbal substance
Herba: Dry extract, extraction solvent: ethanol 50% (V/V)
Dry extract, extraction solvent: water
The European Union herbal monograph refers only to two herbal preparations from Sisymbrii officinalis herba. The justification for proposing only two herbal presentations is presented below.
Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
Flos: In the past, several combination cough products were on the market in Spain which included Erysimum officinale combined with Liquiritiae radix, Althaea radix, Marrubii herba, Anisi fructus and/or Thymi herba.
Herba: The herbal substance is also available in combination products with other herbals or chemical substances (mainly codeine). Erysimum officinale was combined with codeine or with sulfoguajacol and with other herbal substances for example in a syrup and in a pastille until 2004 (Belgium).
1.2. Information about products on the market in the Member States
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
Table 3. Products on the market containing Sisymbrii officinalis herba (dried flowering aerial part) as active herbal substance
1.3. Search and assessment methodology
Literature search was conducted using Pubmed/MEDLINE, TOXNET until the end January 2013 with the search terms “hedge mustard”, “Sisymbrium officinale (L.) Scop.”, “Erysimum officinale L.”.
Literature references of the identified scientific publications and a search in www.google.com were used to look for articles.
Some old references were provided by interested parties during the call for scientific data.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the European Union
Sisymbrium officinale [syn. Erysimum officinale (L.) Scop., Erysimum officinarum Crantz, Erysimum runcinatum Gilib, Chamaeplium officinale Weber) belongs to the Brassicaceae (Cruciferae) family (Hänsel et al. 1994). It is an annual plant of Eurasian origin, which grows in Europe, Asia north- America and
Herba Erisimi is already mentioned in the second edition of the Hagers Handbuch (Frerichs et al. 1949) and it is recommended for laryngeal catarrh, hoarseness. It is drunk by singers before performances as a tea, and it is known as Singer’s plant. According to the Materia Medica Vegatabilis by Steinmetz (1954), Sisymbrium is an expectorant and diuretic, and is recommended for chronic coughs and hoarseness. The sweetened juice is used.
According to the Précis de Matière Médicale by Paris & Moyse (1981), it is as popular remedy against hoarseness and cough as an expectorant; it is mentioned as the ‘Herbe aux Chantres’.
The therapeutic activity of Sisymbrium officinale was attributed to the sulphated components (Paris & Moyse 1981). Historically, the sulphated compounds are reputed to stimulate the mucosal secretion in the upper respiratory tract, so increasing expectoration (Leclerc 1983).
Braun (1981), in his herbal substances’ lexicon, recommends it as
Potter’s New Cyclopedia of Botanical Drugs and Preparations (Wren 1982) recommends the herb as a remedy for hoarseness and weak lungs.
In his Compendium de Phytothérapie (1986), Van Hellemont mentions that the aerial parts of hedge mustard are traditionally used as a remedy for airway ailments such as laryngitis, pharyngitis, coughs and hoarseness including loss of voice, chronic bronchitis and asthma.
This medicinal use can be found in more recent literature as well (Berdonces 1998, Gruenwald et al. 2004). Bruneton (1999) recommends the flower and fresh or dried flowering tops of Sisymbrium for the symptomatic treatment of cough, during acute benign bronchial disease, and locally (collutorium or lozenges) as an antalgic in buccal or pharynx conditions.
2.2. Information on traditional/current indications and specified substances/preparations
Products that fulfil the requirement of thirty years traditional use
Literature:
Comminuted herbal substance (Frerichs et al. 1949, Steinmetz 1954, Wren 1982, Braun 1981, Paris
& Moyse 1981).
Indication: As a diuretic and expectorant, and for chronic coughs, hoarseness and ulceration of the mouth and faces
Liquid extract (Wren 1975, 1982) (1:1) extraction solvent 25% ethanol (based on the current practice at that time in the British Herbal Pharmacopoeia)
Indication: For hoarseness and weak lungs and to recover the voice.
Products on the market according to information by Member States:
1.Dry extract (DER:
This preparation has a marketing authorisation based on
2.Dry extract (DER: 6:1), extraction solvent: water; on the Belgian market since 1962 as a combination product, since 2004 as a
Cough reliever and as a local analgesic in conditions of the oral cavity and/or pharynx.
3.Dry extract (DER:
Product that does not meet the requirements of traditional use for thirty years
1.Dry extract (DER
Traditionally used locally as an analgesic in conditions of the oral cavity and/or pharynx.
Rapporteur’s comment: This product has been registered in France as traditional herbal medicine product. Since the proof for the 30 year traditional use is not available in the public domain, this preparation
Based on the data mentioned above and taking into account the indication accepted by HMPC for other herbal substances with the same properties the following indication is included in the monograph:
Traditional herbal medicinal product is for the relief of throat irritation such as hoarseness and dry cough.
Based on the data provided by Member States, the following herbal preparations are included in the monograph:
a.Dry extract (DER
b.Dry extract (DER:
Assessor’s comment: The dry extract (DER: 6:1), extraction solvent water is covered by the herbal preparation b).
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
Literature
Preparation that fulfils the requirement of thirty years of traditional use:
Potter’s New Cyclopedia of Botanical Drugs and Preparations (Wren 1982):
Liquid extract 1:1) extraction solvent 25% ethanol (based on the current practice at that time in the British Herbal Pharmacopoeia)
dosage:
Rapporteur’s comment: It is not known from the provided posology whether this is a daily dose or a single dose, thus this preparation has not been included in the monograph.
Preparations that do not meet the requirements of traditional use for thirty years
Gran Enciclopedia de las Plantas Medicinales (Berdonces 1998):
Market overview provided by Member States
Products that fulfil the requirement of thirty years traditional use:
1. Dry extract (DER
This herbal preparation has been on the French market since 1959 and in Portugal since 1999. Oromucosal use: a lozenge contains 10 mg of extract
Adults: 10 to 12 lozenges daily (corresponding to
Children over 6 years of age: 5 to 6 lozenges daily (corresponding to
2. Dry extract (6:1), extraction solvent: water
This herbal preparation has been on the Belgian market as a combination product since 1962 and as a
Oral use: syrup which contains 5.50 mg extract/ml;
Adults: 82.5 mg 3 – 4 times daily (corresponding to
Children: 27.5 mg 3 – 4 times daily (corresponding to
Adults: 10 mg
Children from 6 years of age: 10 mg 5
Rapporteur’s comment: this product is covered by the following preparation (dry extract
3. Dry extract
The preparation which is made from the dried herbal substance has been on the German market at least since 1976.
Oromucosal use: a pastille contains 7.5 mg dry extract
Adults and adolescents over 12 years of age: 10 to 12 pastilles daily, 7.5 mg 10 – 12 times daily (corresponding to
Children 5 to 11 years of age: 5 to 6 pastilles daily, 7.5 mg 5 – 6 times daily (corresponding to 225- 360 mg of the herbal substance per day)
Duration of use: no limit
Products that do not meet the requirements of traditional use for thirty years:
Dry extract (DER
Oromucosal use: a lozenge contains 15 mg of extract
Adults: 4 to 6 lozenges daily
Children over 6 years of age: 2 to 3 lozenges daily
Based on the data provided by Member States, the following information on the two herbal preparations are included in the monograph:
Oromucosal use
Adolescents, adults and elderly
a)Dry extract (DER
b)Dry extract (DER
Children 6 – 11 years of age
a)Dry extract (DER
b)Dry extract (DER
The oromucosal use in children under 6 years of age is not recommended.
The tablet/lozenge will dissolve in the mouth without chewing.
Oral use
Adolescents, adults and the elderly
b) Dry extract (DER
Children 3 – 11 years of age
b) Dry extract (DER
The oral use in children under 3 years of age is not recommended.
Duration of use
If the symptoms persist longer than 1 week during the use of the medicinal product, a doctor or a qualified healthcare practitioner should be consulted.
Method of administration
Oromucosal use
Oral use
3. Non-Clinical Data
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Primary pharmacodynamics
Antimicrobial/antifungal activity
The antimicrobial activity of an aqueous dry extract (DER: 4:1) of the dry aerial parts of Sisymbrium officinale was tested in the range of
Hedge mustard volatiles were isolated from fresh and dried material by different methods i.e. hydrodistillation (without and upon autolysis). Autolysis was performed prior to hydrodistillation in order to allow natural plants enzymes to liberate bound volatiles from
All hydrodistillates exhibited antibacterial activity against five
Volatiles isolated from fresh plant material (without and upon autolysis) showed higher antimicrobial activity than dried plant material against all bacterial and fungal strains (see Table 4).
Table 4. (Blazević et al., 2010)
Antimicrobial activity of volatiles obtained by hydrodistillation
According to Blazević et al. (2010), the observed antimicrobial activity is due to the isothiocyanates and nitrils content of the plant. In addition alcohols and aldehydes, fatty acids and corresponding esters also can contribute to this activity. These components are present in different percentage in the fresh and the dried plant material.
The
(SOw_s) and a precipitate (SOw_p). Further fractionation of Sow_s allowed the identification of adenine, adenosine, and guanosine that were present in significant quantities only in the traditionally prepared aqueous extract. Polysaccharides were detected in the Sow_p fraction. They all were tested for the topical
2,000 µg/cm2, SOw_s 26% at 1,000 µg/cm2 and SOw_p 14% at 1,000 µg/cm2) (Politi et al. 2008).
Secondary pharmacodynamics
Myorelaxant activity
In isolated
Antimutagenic activity
In preliminary experiments the above mentioned extract of Sisymbrium officinale showed lack of mutagenic effects in the range of concentrations tested
Escherichia coli WP2uvrA and in Salmonella typhimurium TA98 respectively (Di Sotto et al. 2010).
Glucoputranjivin and isopropyl isothiocyanate were isolated from an aqueous dry extract (4:1) of the dry aerial parts of Sisymbrium officinale. The antimutagenic activity of these compounds was evaluated in a bacterial reverse mutation assay using E. coli WP2, WP2uvrA, and WP2uvrA/pKM101 strains, in comparison with the extract. In the absence of the exogenous metabolic activation system S9, the thio compounds exerted antimutagenic activity against the
Safety pharmacology
No data are available.
Pharmacodynamic interactions
No data are available.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data are available.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
No toxicological data have been found on the herbal substance.
Only some toxicological data can be found for the cardiac glycoside, Helveticosid
LDL0 i.v.: pigeon 0.285 mg/kg, guinea pig 0.867 mg/kg, cat 0.106 mg/kg, monkey 0.103 mg/kg
LD50 i.v.: rat 54 mg/kg, i.p. mice 7.8 mg/kg.
Rapporteur’s comment: LDL0: Lethal Dose Low: Lowest dose of a substance reported to have caused death in humans or animals.
3.4. Overall conclusions on non-clinical data
Results from relevant experimental studies on Sisymbrium officinale to support the proposed indication are very limited. The reported pharmacological effects are not considered contradictory to the traditional uses.
Specific data on pharmacokinetics and interactions are not available.
Content of cardiac steroid glycosides (cardenolides) in the tips of the flowering plant of Sisymbrium officinale was measured to be 49.8 mg/100 g after extraction with chloroform (Larowski et al. 1979).
The recovery of cardenolides is low after extraction with water. If the cardenolides content of the aqueous extract is ≤1ppm, a lozenge containing 10 mg extract would contain less than 10 ng cardenolides. The daily amount of lozenges is up to 12 that means maximum 120 ng cardenolides. In various publications it is assumed that the oral resorption of strophantin is poor (~20%). That would mean that the daily dosage would be around 24 ng cardenolides. For the oral use, the maximum daily dose of cardenolides would be (82.5×4)/0.2 is 66 ng. This is substantially lower than the minimum therapeutic i.v. dose of
Based on this calculation it can be concluded that there are no safety concerns relating to the use of the preparations in the given indication at the traditionally used doses. During the
As there is no information on reproductive and developmental toxicity the use during pregnancy and lactation cannot be recommended.
Tests on genotoxicity and carcinogenicity have not been performed. The requirements for the establishment of a European Union list entry are not fulfilled.
4. Clinical Data
4.1. Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No data are available.
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No data are available.
4.2. Clinical Efficacy
4.2.1. Dose response studies
No data are available.
4.2.2. Clinical studies (case studies and clinical trials)
Clinical studies with products containing hedge mustard have not been found in the literature.
4.2.3. Clinical studies in special populations (e.g. elderly and children)
No data are available.
4.3. Overall conclusions on clinical pharmacology and efficacy
Clinical studies with products containing hedge mustard have not been found in the literature.
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No data are available.
5.2. Patient exposure
Clinical studies with products containing hedge mustard have not been found in the literature.
5.3. Adverse events and serious adverse events and deaths
No side effects have been reported (Hänsel et al. 1994).
No adverse effects were reported from the Belgian, French, Portuguese and German market overview.
Wording in the European Union herbal monograph
Not known.
5.4. Laboratory findings
No data are available.
5.5 Safety in special populations and situations
Contraindications
Information from the package leaflet of a Belgian product: Hypersensitivity
Warnings
Information from the package leaflet of a German product:
The use in children under 5 years of age is not recommended due to lack of adequate data.
Information from the package leaflet Belgian product:
Pastille should not be used under 6 years of age.
Syrup should not be used by children under 3 years of age.
Information from the package leaflet of a French product:
Due to the pharmaceutical form (solid dosage form) all the products are not to be used for children under 6 years of age.
Wording in the European Union herbal monograph
The oromucosal use in children under 6 years of age is not recommended because of the pharmaceutical form (solid dosage form) and due to the lack of adequate data on liquid preparations.
The oral use in children under 3 years of age is not recommended due to lack of adequate data and because medical advice should be sought.
Fertility, pregnancy and lactation
Information from the package leaflet of Belgian product:
The use of the syrup is not contraindicated during pregnancy and lactation.
Information from the package leaflet of a German product:
Safety during pregnancy and lactation has not been established. In the absence of sufficient data, use during pregnancy and lactation is not recommended.
Wording in the European Union herbal monograph
Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended.
No fertility data available.
Warnings
Information from the package leaflet of a German product:
The drug contains <1 ppm cardiac steroid glycosides. Caution by heart drug digitalis or digoxin, in potassium deficiency or in chronic inflammation in the mouth and pharynx.
Rapporteur’s comment: Interaction with digitalis or digoxin or potassium deficiency is only a theoretical assumption.
According to the literature (Hänsel et al. 1994) adverse effects have not been reported.
Wording in the European Union herbal monograph
If the symptoms worsen during the use of the medicinal product, a doctor or a qualified healthcare practitioner should be consulted. If dyspnoea, fever or purulent sputum occurs, a doctor or a qualified healthcare practitioner should be consulted immediately.
Interactions
Information from the package leaflet of a German product:
Potassium deficiency.
Intake of cardiac glycosides.
Rapporteur’s comment: This is only a theoretical assumption; no report or pharmacoviligance case is known according to information provided by the Member States.
Wording in the European Union herbal monograph
Not reported.
Overdose
Information from the package leaflet of a German product:
There is no information about overdose.
Hagers Handbuch (Hänsel 1994), PDR for Herbal Medicines (Gruenwald et al. 2004):
It is conceivable that over dosage would have
Cases of poisonings, however, have not been recorded.
Wording in the European Union herbal monograph
No case of overdose has been reported.
5.5. Overall conclusions on clinical safety
The medicinal use of hedge mustard preparation is considered safe because no adverse effects have been reported during the
The content of cardiac steroid glycosides measured in the aqueous extract is too low to present any risk to human health. A limit of ≤1ppm for the cardenolides content is included into the monograph.
The oromucosal use in children under 6 years of age is not recommended because of the solid dosage form and due to lack of adequate data for the liquid pharmaceutical forms.
The oral use in children under 3 years of age is not recommended due to lack of adequate data and because, for the proposed indication, medical advice should be sought for this age group.
Since there are insufficient data, the use during pregnancy and lactation is not recommended.
6. Overall conclusions
Sisymbrii officinalis herba has been in medicinal use for a period of at least 30 years as requested by Directive 2004/24/EC, thus the requirement for the qualification as a traditional herbal medicinal product is fulfilled
Traditional herbal medicinal product for the relief of throat irritation such as hoarseness and dry cough.
Since clinical studies with products containing hedge mustard have not been found in the literature
The pharmacological studies on the
The plausible effect of the herbal substance on the pharyngeal irritation might be due to the high mucilage’s content
For the water extracts and their corresponding posology, there are no safety concerns due to the low cardenolide (cardiac steroid glycosides) recovery with the aqueous extraction. A limit of ≤1ppm for the cardenolides content is included into the monograph.
The oromucosal use in children under 6 years of age is not recommended because of the pharmaceutical form (solid dosage form) and due to lack of adequate data for the liquid pharmaceutical forms.
The oral use in children under 3 years of age is not recommended due to lack of adequate data and because medical advice should be sought.
In the absence of sufficient data, the use during pregnancy and lactation is not recommended.
Due to the lack of data on genotoxicity, the inclusion of Sisymbrii officinalis herba in the European Union list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products cannot be recommended.