Solidago – European Goldenrod (Solidaginis virgaureae herba)
|Latin name of the genus:||Solidago|
|Latin name of herbal substance:||Solidaginis virgaureae herba|
|Botanical name of plant:||Solidago virgaurea l.|
|English common name of herbal substance:||European goldenrod|
Latin name of the genus: Solidago
Latin name of herbal substance: Solidaginis virgaureae herba
Botanical name of plant: Solidago virgaurea L.
English common name of herbal substance: European Goldenrod
- ASSESSMENT REPORT
- FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S) OR COMBINATIONS
- THEREOF WITH TRADITIONAL USE
- Solidago virgaurea L., herba
- I.REGULATORY STATUS OVERVIEW1
- Solidaginis herba
- Solidaginis herba
- Solidaginis herba
- II.ASSESSMENT REPORT FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S) OR COMBINATIONS THEREOF WITH WELL- ESTABLISHED USE AND/OR TRADITIONAL USE
- II.1 INTRODUCTION
- II.3 PHARMACOLOGY
- II.18.104.22.168 Antioxidant activity
- II.22.214.171.124 Analgesic activity
- II.126.96.36.199 Spasmolytic activity
- II.188.8.131.52 Antibacterial activity
- II.184.108.40.206 Antifungal activity
- II.220.127.116.11 Anticancer activity
- II.18.104.22.168 Immunobiological activity
- II.22.214.171.124 Diuretic activity
- II.3.3 Pharmacokinetics
- II.3.4 Toxicology
- II.3.4.1 Cytotoxicity
- EC50 values (concentration (μM) that caused 50% inhibition of cell growth in vitro.
- Acute Toxicity
- Table 11. Presentation of the non–randomized open clinical studies with Solidago virgaurea products.
- II.4.2.1 Clinical studies in special populations (e.g. elderly and children)
- II.4.2.2 Assessor’s overall conclusions on clinical efficacy
- II.4.3 Adverse events
- II.4.4 Interactions
- II.4.5 Assessor’s overall conclusions on clinical safety
- II.4.6 Use in pregnancy and lactation
- II.4.7 Overdose
- II.4.8 Effects on ability to drive or operate machinery
- II.4.9 Contraindications
- II.4.10 Overall conclusions on safety
FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S) OR COMBINATIONS
THEREOF WITH TRADITIONAL USE
BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC AS
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
II. Combination products. Average number of combination substances:
1)Herbal tea – Filipendulae ulmariae herba, Salicis cortex, Violae tricoloris herba, Harpagophyti radix, Equiseti herba,
Solidaginis herba, Callunae herba – on the market since 1999; for oral use; indications – as an adjuvant for inflammatory and degenerative diseases of locomotors apparatus (rheumatism, arthrosis, arthritis and gout), adjuvant therapy in flu like symptoms
2)Herbal tea – Epilobii herba, Bucco folium,
Solidaginis herba, Calendulae flos cum calyce – on the market since 1999; for oral use; indication- for adjuvant therapy in case of micturition difficulties (e.g. associated with diagnosed benign prostate hyperplasia, prostatitis, inflammations of the urinary tract; special warning: not recommended for patients with chronic renal diseases, regular medical supervision is required!
3)Herbal tea – Uvae ursi folium, Equiseti herba, Myrtilli herba, Matricariae flos, Sambuci nigrae flos,
Solidaginis herba, Thymi herba; – on the market since 1989, for oral use; indications – as an adjuvant therapy in acute and chronic infections and inflammations of the urinary tract.
ASSESSMENT REPORT FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S) OR COMBINATIONS THEREOF WITH WELL- ESTABLISHED USE AND/OR TRADITIONAL USE
Solidago virgaurea L. (synonyms: Amphiraphis leiocarpa, Amphiraphis pubescens, Dectis decurrens, Doria virgaurea, European golden rod) belongs to the family of Asteraceae (Compositae). The herbal substance consists of the dried, flowering parts of the plant (Solidaginis virgaureae herba, British Herbal Pharmacopoeia 1976; ESCOP Monographs 2003; Bader 1994; 1999; 2006; Goldenrod. http://www.Herbalgram.org; Hoppe 1975; PDR for Herbal Medicines 2000; Pharmeuropa 2001;
Solidago has been used for treatment of different diseases in Europe since medieval times (Arnold from Villanova
European goldenrod contains miscellaneous flavonoids (1.5%) (quercetin, kaempferol and their glycosides, astragalin and rutoside) and antocyanidins, derivatives of cyanidin. Other constituents include triterpene saponins of the oleanane type (up to 2%), the bisdesmosidic phenol glycosides leiocarposide
The pharmacological and clinical effects of Solidago virgaurea has been described in several reviews (Bader 1999; Hiller and Bader 1996; Laszig et al. 1999, Melzig 2004, Schilcher 1987; Schilcher 1999, Schmitt 1996; Weiss 1980; Yarnell 2002).
A synergic action of several components of the Solidago virgaurea L. is proposed. Therefore, the herbal substance or herbal preparations from Solidago must be considered as the active ingredient.
Terpene fraction or its derivatives were shown to present antiulcer activity. Such activity was described for a labdane diterpene from Solidago chilensis in HCl/ethanol induced gastric lesions in mice
In experiment on rats the combined preparation of Solidago virgaurea, Fraxinus excelsior and Populus tremula (Phytodolor®) was tested for an
Extracts of Solidago virgaurea (aqueous/alcoholic) were tested for
Saponins, flavonoids and caffeic acid esters from Solidago virgaurea inhibited the activity of leukocyte elastase, a protease involved in the progression of inflammation. The ester saponins increased permeability of cells and stimulated the synthesis and release of glucocorticoids in the adrenal glands (Melzig et al. 2000).
The pharmacological activity and toxicology of phytotherapeutic Ariven® composed of aqueous extract of Solidago virgaureae, extr. Oleandris, sparteine sulfate,
II.126.96.36.199 Antioxidant activity
Chlorogenic and caffeic acids have been reported to scavenge reactive species of oxygen and nitrogen (Kono et al. 1997).
Mixture of the ethanolic extracts (35% aqueous ethanol) from dried Solidago virgaurea, Potentilla anserina, Radix Rubiae tinctorum, Equisetum arvense, Oleum Juniperi and Petroselini sativi fructus was used in vitro to estimate glucose consumption by rabbit brain slices. Swelling of brain slices in vitro was significantly diminished with an increase of glucose consumption and the aerobic formation of lactic acid (Dittmann 1973).
Antioxidant activity of ethanolic extract of Solidago virgaurea (0.52 mg/ml of rutin, 0.64 mg/ml of flavonoids and ethanol 45.6% v/v) was tested in vitro as a component of the phytotherapeutic drug Phytodolor®. The activity of xanthine oxidase (XOD), diaphorase
Similar effects of Phytodolor® were described in another series of experiments (Germann et al. 2005).
II.188.8.131.52 Analgesic activity
Analgesic activity of leiocarposide was shown in experiments performed on mice in hot plate and withdrawal of a hind foot upon irradiation (the inhibition of a polysynaptic reflex) tests. This activity was compared with aminophenazone effects (Table 3, Metzner et al. 1984).
Table 3. Analgesic activity of leiocarposide and aminophenazone in mice (Metzner et al. 1984).
The analgesic potential of Solidago virgaurea was tested in vitro for affinity to three neuropeptide receptors involved in the mediation of acute pain in mammals: bradykinin, expressed in Chinese hamster ovary cells, neurokinin 1 expressed in astrocytoma cells and calcitonin gene related peptide. The Solidago methanolic extract of the seeds of the plant produced significant inhibition of radio- ligand binding for bradykinin receptors (Sampson et al. 2000).
II.184.108.40.206 Spasmolytic activity
In experiment performed in vitro on isolated smooth muscles of intestines of guinea pig Solidago virgaurea ethanolic extract induced spasmolytic activity in the range of 14.73% of papaverin (Westendorf and Vahlensieck, 1981).
Presence of flavonoids (quercetin and kaempferol) in Solidago virgaurea preparations may contribute to explain vascular smooth muscle relaxation. It can be concluded that vasodilatatory action depends on the inhibition of protein kinase C, inhibition of cyclic nucleotide phosphodiesterase or decrease of Ca2+ uptake (Rácz et al. 1980; Duarte et al. 1993).
In other experiments performed in vitro in acetylcholine pretreated urinary bladder of the rat the phytotherapeutic product Urol®) combined of Extr Rad. Rubiae tinct. Spir, Extr. Sem Ammeos visnagae spir., Extr. Herb. Solidago virgaureae spir., Extr. Rad. Taraxaci and aescin exhibited spasmolytic activity. This effect was mainly due to the ingredient Extr. Solidago virgaureaeWestendorf and Wahlensieck 1983).
Aqueous extract of leaves of Solidago virgaurea (aqueous extraction, evaporation of eluate to a spissum extract and dilution with water) inhibited muscarinic M2 and M3
II.220.127.116.11 Antibacterial activity
Antibacterial activity of monovalent preparations (six extracts) and mixtures (ten preparations) of Solidago virgaurea were tested in vitro against urogenital bacterial pathogens (Staphylococcus aureus, Staphylococcus epidermidis). Tested mixtures (Solidago virgaurea combined with Cortex Rhus aromaticae, Fol. Uvae ursi and Hb. Taraxaci) showed significantly stronger antibacterial activity than monovalent preparations. The results indicate that Solidago virgaurea extracts exhibited antibacterial effect against Staphylococcus aureus and Staphylococcus epidermidis. Moreover these extracts of
Solidago virgaurea demonstrated activity against a larger range of microbes than extracts of Solidago gigantea and Solidago canadensis (Brantner 1999).
Antimicrobial activity of ethanolic and methanolic extracts of Solidago virgaurea L. were tested in vitro by use of
Table 4. Antimicrobial activity (MBC) of extracts from plant and callus of Solidago virgaurea L. from in vitro cultures (Thiem and Goślińska 2002).
MBC – minimal bactericidal concentration (mg/ml); – no activity
Inhibition of dihydrofolate reductase activity, an enzyme modulating cytostatic
activity was found in in vitro experiments with
Solidago virgaurea ethanolic extract (rutin 0.52 mg/ml, flavonoids 0.64 mg/ml, ethanol 45.6% v/v,
(I50=0.013% v/v). However, the overall effect of the combination was more pronounced. The single component as the combined extracts exhibited activity in the range of effective NSAID’s (Strehl et al. 1995).
II.18.104.22.168 Antifungal activity
In the course of screening for new antifungal agents Bader et al. (1987) showed that deacylated triterpenoid saponins of Solidago virgaurea, isolated after mild alkaline hydrolysis of the mixture of genuine ester saponins, showed higher activity against several Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis, Candida pseudotropicalis, Candida guilliermondi, Candida glabrata and Cryptococcus neoformans), than the mixture of ester saponins. These deacylated saponins (bisdesmosidic glycosides of polygalacic acid) virgaureasaponins 1, 2 and 3 (Bader et al. 1992) demonstrated higher antifungal activity than that of the corresponding prosapogenins (monodesmosides) (Bader et al 1990b).
In other experiments Pepeljnjak et al. (1998) showed antimycotic activity of Solidago virgaurea ethanolic extract against dermatophytes, especially against Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis. Antifungal activity against Candida albicans was very low.
II.22.214.171.124 Anticancer activity
Significant tumour inhibitory action of Virgaurea saponin E (1 mg/kg/day) was found in vivo in mice in allogenic
In an SCID mouse model antineoplastic activity of Solidago virgaurea on prostatic tumour cells was tested and cytotoxic activity on various tumour cell lines was demonstrated (human prostate, breast, melanoma and small lung carcinoma). The active fraction of the extract corresponding to a molecular weight of 40,000
II.126.96.36.199 Immunobiological activity
Immunomodulatory (induction of macrophages and activation of
Further chromatographic separation demonstrated the presence of five benzylbenzoates from the hexane soluble fraction of the methanolic extract of the aerial parts of Solidago virgaurea var. gigantea. By using in vitro mouse peritoneal macrophages two compounds
function (range of
II.188.8.131.52 Diuretic activity
The diuretic properties of Solidago spp. are in prevalence based on studies performed on the European goldenrod (S. virgaurea L.). Leiocarposide
The leiocarpic acid
Table 5. Diuretic activity of leiocarposide and furosemide in rats (Chodera et al. 1985a, b).
Table 6.Diuretic activity of leiocarposide after intraperitoneal (i.p.) and oral (per os) administration (Chodera et al. 1985 b).
Table 7. Elimination of sodium, potassium and calcium ions in urine of the control, leiocarposide and furosemide treated rats (Chodera et al 1985b).
The flavonoid fraction of Solidago virgaurea L. administered to rats showed an increase of diuresis (88% after 24h). Decrease of an overnight excretion of potassium and sodium and increase of excretion of calcium ions was observed (Table 8, Chodera et al. 1991).
Table 8. Diuretic and saluretic activity of the flavonoid fractions of Solidago virgaurea (Chodera et al. 1991).
Interestingly, it was also demonstrated, that leiocarposide diuretic activity was reduced by the presence of flavonoids and saponins. In contrary, some researchers suggest that diuretic activity of goldenrod is exerted by the mixture of flavonoids and saponins, but the others demonstrated in animal studies relative inactivity of flavonoid mixture (Schilcher et al. 1989).
In experimentally induced renal calculi model in rats it was shown, that after 6 weeks of administration of leiocarposide (25 mg/kg) the growth of the renal calculi was significantly decreased (Chodera et al. 1988).
Significant increase of diuresis in rats together with an increased elimination of sodium, potassium and chloride ions was observed after oral administration of infusion of Solidago virgaurea (0.3% of flavonoids, 4.64 ml/kg and 10.0 ml/kg). The lower dose was more efficient (Schilcher and Rau 1988).
Acylated triterpenoid saponins (especially virgaureasaponin B) present in Solidago virgaurea could transiently change the cell membrane permeability and induced alterations in ionic homeostasis with enhanced permeability between the intracellular and extracellular compartments. These effects could be the result of the structural similarity of acyl groups with fatty acids as constituents of the biological membranes (Melzig et al. 2001).
Comparison of diuretic activity of different fractions of Solidago virgaurea extracts (methanol/water, 70:30) on Sprague Dawley rats
The hydroxycinnamic acid fraction (100 mg/kg p.os) significantly increased sodium and potassium excretion in urine. This activity did not differ from furosemide efficacy 10 mg/kg/. There was no influence on calcium ion excretion, both in hydroxycinnamic acid and furosemide groups.
The flavonoid fraction (100 mg/kg) did not elevate urine volume or ion secretion. The significant increase of urine volume and saluretic activity for sodium and potassium ions was demonstrated for the saponin fraction (25 mg/kg – 100 mg/kg). These effects were comparable to those of furosemide (10 mg/kg per os) (Kaspers et al. 1998).
Active flavonoides of Solidago virgaurea (especially quercetin) inhibit NEP and angiotensin- converting enzyme (ACE) activity (Schilcher and Rau 1988; Melzig et al. 2001a; Melzig and Major 2000; Table 9, Major 2001
Table 9. Influence of the methanol extracts of Solidago virgaurea and their fractions on activity of neutral endopeptidase (NEP) (Major 2001,
The mechanism of beneficial renal and cardiovascular activity of Solidago virgaurea can depend on modulation of neutral endopeptidase activity (NEP). By blocking the hydrolysis of the vasoactive peptides, Solidago treatment can regulate water and sodium balance and cardiovascular homeostasis by increasing water and sodium excretion and arterial and venous vasodilatation (Melzig and Major 2000).
A selection of several herbal medicinal products was analysed for their modulatory influence on expression of cytochrome
There are no specific data on pharmacokinetics of Solidago virgaurea. However, some interactions are possible due to influence on CYP3A4 genes expression.
Constituents of the aerial parts of the plant Solidago virgaurea var. gigantea used as stomachic and diuretic in Korea were identified by chemical and spectroscopic methods. Six terpenoids and four phenolics were isolated from the
Table 10. Cytotoxic effects of Solidago virgaurea constituents (Choi et al. 2004).
EC50 values (concentration (μM) that caused 50% inhibition of cell growth in vitro.
Other investigations on the constituents Solidago virgaurea var. gigantea revealed isolation of three cytotoxic compounds:
No data available. Acute toxicity of the leiocarposide in rats was reported: LD50 (oral) as 1.55 g/kg b.w. (Chodera 1985a).
No information on genotoxicity and carcinogenicity is available.
No data are available on reproductive or developmental toxicity.
No relevant data are available on toxicology of Solidago virgaurea except of acute toxicity of leiocarposide. Because of the lack of data concerning mutagenicity and genotoxicity, the inclusion of Solidago virgaurea L. to the Community List cannot be considered.
In an open post marketing crossover study with placebo in 22 healthy patients (age 17 – 61 years), an ethanolic extract made from fresh plant Solidago virgaurea L. was tested. The patients received 100 (5×20) drops/day of the ethanolic extract (64 % V/V, Goldruten Tropfen®) for 2 days. In Solidago treated groups the significant increase of daily volume of urine (27%) was observed (p<0.01)
In an open multicentre postmarketing study the ethanolic extract of Solidago virgaurea L. made from fresh plant (64 Vol%, Goldruten Tropfen®) was tested in 53 patients (45 female, 8 male, age: 6 – 83 years) with symptoms of urinary tract inflammation: dysuria, pollakisuria, tenesmus. The treatments lasted 1 year, but time of the treatment of individual patient differed, depending on the physician´s decision. The patients with renal stones, renal carcinoma, gonorrhoea, syphilis, AIDS and marked prostate hyperplasia were excluded, as patients with bacterial counts in urine over 104. Adult patients
received 100 drops (5×20) of Solidago extract. Patients younger than 12 years received 55 drops/day. After treatment in 65.4% treated patients the significant clinical improvement was observed with significant reduction of dysuria, pollakisuria and tenesmus
The efficacy of the dry extract of Solidago virgaurea (5.4:1, Stromic®) was tested in an open multicentre study performed by 289 physicians in 745 female patients (age:
In the postmarketing study performed on 1487 patients with several urinary tract diseases (irritable bladder, urinary tract infections, renal calculi/gravel) the efficacy of an extract from Solidago virgaurea
In an open multicentre (308 physicians) study performed on 1487 patients with chronic recurrent irritable bladder condition the subgroup of 512 patients (age: 13 – 96 years, 77% female) was treated for five weeks. The patients received Solidago virgaurea L. dry extract
The case report of patients treated with Solidago virgaurea dry extract for 4 weeks after extracorporeal shock wave lithotripsy resulted with spasmolytic effects, and lack of additional spasmolytic treatment needed (Laszig et al. 1999).
An open outpatient study was performed in 20 patients with renal calculi/gravel (age: 7 – 60 years) to test therapeutical efficacy of phytomedicine Fitolizyna® (Solidago extract as one of the components) for 2 weeks – 3 months (1 teaspoon of paste, three times daily). Significant diuretic effect was noted in all tested patients with very good tolerance of treatment (Krzeski 1960).
In patients with different subtypes of rheumatic diseases the
(Phytodolor®) have shown a similar efficacy compared to NSAID treatment (Chrubasik and Pollak 2003; Ernst 2004; Jorken and Okpanyi 1996;
However, the relevant participation of Solidago virgaurea in clinical efficacy of composition products is not known.
Table 11. Presentation of the
non–randomized open clinical studies with Solidago virgaurea products.
II.4.2.1 Clinical studies in special populations (e.g. elderly and children)
No relevant data available. No special studies for children and elderly were performed. The number of children included into studies is to small for further assessment. Products containing Solidago virgaurea L. cannot be recommended for use in children below the age of 12 years.
II.4.2.2 Assessor’s overall conclusions on clinical efficacy
Solidago virgaurea products were used in 5
Overall, in the presence of missing information, assessing and interpreting treatment effects of Solidago virgaurea can be limited only to traditional use.
II.4.3 Adverse events
Hypersensitivity reactions and mild gastrointestinal disorders (in
Patients suffering from allergic contact dermatitis due to Compositae species are requested to avoid contacts with Solidago virgaurea (De Jong et al. 1998; Lundh et al. 2006; Myers and Wohlmuth 2005; Schätzle et al. 1998, Stingeni et al. 1999, Zeller et al. 1985).
No data available.
II.4.5 Assessor’s overall conclusions on clinical safety
No case reports on adverse reactions or other signals of safety concern in connection with Solidago virgaurea L., inflorescences were identified, except in patients allergic to Compositae species. As there is no information on reproductive and developmental toxicity the use during pregnancy and lactation cannot be recommended.
II.4.6 Use in pregnancy and lactation
No data available.
No data available.
II.4.8 Effects on ability to drive or operate machinery
No data available.
Known hypersensitivity or allergy to Compositae (Asteraceae) or Solidago spp.
II.4.10 Overall conclusions on safety
As there is no information on reproductive and developmental toxicity the use during pregnancy and lactation cannot be recommended.
The traditional medicinal use of Solidago virgaurea L. has been documented within the Community. No specific clinical data of Solidago virgaurea L. adverse effects have been identified under normal conditions of use. Two
As no data on use in children are available, products containing Solidago virgaurea L. cannot be recommended for use in children below the age of 12 years.
The traditional use of Solidago virgaurea L. is well documented. However, because of absence of sufficient clinical data, the quality of the available studies cannot be evaluated. The results of clinical trials cannot support a
Although this phytotherapeutic treatment in urinary tract diseases is extremely popular, there is no detailed reasonable scientific explanation on effects and the exact mechanism of diuretic action.
No isolated compound which has been isolated from Solidago virgaurea is recognized as responsible for its diuretic action, thus the complex mixture of constituents contributed to this effect.
Indication of an increase of volume of urine, especially in cases of inflammation and renal calculi/gravel is well documented, both in monographs and textbooks, as in data regarding longstanding use.
The therapeutic dose is
There is almost no information on the toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicology. Therefore the use in pregnancy and lactation is not recommended.
The use in children under 12 years of age is not recommended, as no data are available on safety of treatment.
Products containing Solidago virgaurea L. are available in many Member States of the EU. Thus, the requirement of medicinal use for at least 30 years (15 years within the Community), Directive 2004/24/EC is fulfilled.
Because of lack of data concerning mutagenicity, the inclusion of Solidago virgaurea L., herba to the Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products cannot be considered.