Urtica – Nettle Leaf (Urticae folium)
|Latin name of the genus:||Urtica|
|Latin name of herbal substance:||Urticae folium|
|Botanical name of plant:||Urtica dioica l.; urtica urens l.|
|English common name of herbal substance:||Nettle leaf|
Latin name of the genus: Urtica
Latin name of herbal substance: Urticae folium
Botanical name of plant: Urtica dioica L.; Urtica urens L.
English common name of herbal substance: Nettle Leaf
1.1.Description of the herbal substance(s), herbal preparation(s) or combinations thereof . 7
1.2.Information on period of medicinal use in the Community regarding the specified
- Regulatory status overview1
- Products on the market:
- Overview of the German Market (from German authority)
- 1. Introduction
- 1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
- Preparations mentioned in the Monograph because they met the requirement of 30 years:
- 1.2. Information on period of medicinal use in the Community regarding the specified indication
- 1.3. Type of tradition, where relevant
- 1.4. Evidence regarding the indication/traditional use
- Four different areas of indication are mentioned in the literature on nettle leaves
- 1.5. Evidence regarding the specified posology
- Accepted posology in the Monograph
- 1.6. Evidence regarding the route of administration
- 1.7. Evidence regarding the duration of use
- 1.8. Assessor’s overall conclusion on the traditional medicinal use
- 2. NON-CLINICAL DATA
- 2.1. Pharmacology
- 2.1.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 2.1.2. Assessor’s overall conclusions on pharmacology
- 2.2. Pharmacokinetics
- 2.2.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 2.2.2. Assessor’s overall conclusions on pharmacokinetics
- 2.3. Toxicology
- 2.3.1. Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 2.3.2. Assessor’s overall conclusions on toxicology
- 3. CLINICAL DATA
- 3.1. Clinical Pharmacology
- 3.1.1. Pharmacodynamics
- 3.1.2. Pharmacokinetics
- 3.2. Clinical Efficacy
- 3.2.1. Dose response studies
- 3.2.2. Clinical studies (case studies and clinical trials)
- 3.2.3. Clinical studies in special populations (e.g. elderly and children)
- 3.2.4. Assessor’s overall conclusions on clinical efficacy
- 3.3. Clinical Safety/Pharmacovigilance
- 3.3.1.Patient exposure
- 3.3.2.Adverse events
- 3.3.3. Serious adverse events and deaths
- 3.3.4. Laboratory findings
- 3.3.5. Safety in special populations and situations
- 3.3.6. Assessor’s overall conclusions on clinical safety
- 4. ASSESSOR’S OVERALL CONCLUSIONS
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
Products on the market:
The assessment of nettle leaf is based on the following literature
Articles supplied by ESCOP (1997, 2003).
Mongraphs on Nettle: Hagers Handbuch (Blaschek W et al 1998), Commission E Monograph (Blumenthal 1998), HerbalGram (American Botanical Council), HerbMed, Tropical Plant Database (Rain Tree Nutrition), MDidea.
Review articles to be mentioned: Chrubasik JE 2007, Setty AR and Sigal LH 2005, Lutomsky J and Speichert H 1983. Szendrei K,
Articles and references retrieved from databases (Pubmed, Toxnet) or internet sources (e.g. Google) until the end of April 2008.
A major problem in assessment of literature on nettle is the issue, that there is not always a clear differentiation between nettle herb and nettle leaf.
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Urticae folium, cut as herbal tea (product on the German market since at least 1976)
ESCOP (ESCOP 1997, ESCOP 2003), Hagers Handbuch (Blaschek W et al, 1998) Herbal Drugs and Phytopharmaceuticals (Wichtl M, 2004)
European Pharmacopoeia 5.6: Whole or cut dried leaves of Urtica dioica L., Urtica urens L., or a mixture of the 2 species.
Nettle leaf consists of the whole or cut, dried leaves of Urtica dioica L., Urtica urens L., their hybrids or mixtures. (Deutsches Arzneibuch 10, Ausgabe 1991)
Comminuted herbal substance for tea.
Commission E Monograph (Blumenthal M et al, 1998)
(1:5) extraction solvent 96% ethanol: water: wine 16.5% (V/V) (1.65:1.35:7) (product on the German market since at least 1976)
Tincture/Spiritus (1:10): (Fintelmann V et al, Phytotherapy Manual 1989)
Rapporteur’s comment: This preparation is not mentioned in the monograph, because its effect is not plausible. For reasoning see ‘II.1.4. Evidence regarding the specified posology’.
Dry extracts prepared with:
dry extract from Urticae folium
dry extract from Urticae folium
dry extract from Urticae folium
dry extract from Urticae folium
or filmcoated tablet containing 600 mg dry extract each (product on the German market since 2007)
dry extract from Urticae folium
Preparations mentioned in the Monograph because they met the requirement of 30 years:
Herbal substance Cut, dried leaves
a)comminuted herbal substance
b)liquid extract from Urticae folium extraction solvent 96% ethanol: water: wine 16.5% (V/V) (1.65:1.35:7)
c)dry extract from Urticae folium
d)dry extract from Urticae folium
e)dry extract from Urticae folium
f)combinations of herbal substance(s) and/or herbal preparation(s)
1.2. Information on period of medicinal use in the Community regarding the specified indication
Lutomsky J and Speichert H, 1983: “Nettle was already known in the ancient times. The ancient Greeks were familiar with its effects. Dioscorides wrote about it in his work. He regarded it as tonic, diuretic, digestive,
Herbal Gram: The Journal of the American Botanical Council: Herb and leaf:
“Stinging nettle herb has been used since ancient times. “Greek physicians Dioscorides (first century C.E.) and Galen (ca.
In Germany, stinging nettle herb is licensed as a standard herbal tea for diuretic action. It is also used as a component of prepared medicines intended for supportive treatment of rheumatic ailments and irrigation therapy in inflammatory conditions of the lower urinary tract (Wichtl and Bisset, 1994). Stinging nettle herb is used in German homeopathy in treatments for urticaria, herpes, eczema, hypersensitive reactions in the skin and joints, and burns (List and Hörhammer, 1979).
In traditional African medicine the herb is used as a snuff powder for nosebleeds, excessive menstruation, and to treat internal bleeding. It is applied on burns (List and Hörhammer, 1979).
In India, the Ayurvedic Pharmacopoeia lists stinging nettle herb for uterine hemorrhage, cutaneous eruptions, infantile and psychogenic eczema, and nosebleed, applying dosages of
Stinging nettle is also widely used in North American aboriginal medicines. People of the Hesquiat, Sanpoil, Shuswap, and Tainarna nations use it as an antirheumatic drug (Moerman, 1998; Palmer, 1975; Smith, 1973; Turner and Efrat, 1982; Ray, 1933). It is also used as a gynecological aid by women of the Cowlitz, Cree, Kwakiutl, Lummi, Quinault, and Squaxin nations. It is taken as an aqueous infusion during childbirth to relax the muscles. The plant juice is taken by pregnant women who are overdue and the tips of the plant are chewed by women during labour (Gunther, 1973; Leighton, 1985; Moerman, 1998; Turner and Bell, 1973; Turner and Efrat, 1982).
In the United States, stinging nettle herb is used as a component in a wide range of dietary supplements. It is also used during and following birth and during lactation in traditional women’s tonic formulas. It is prescribed by naturopathic physicians and licensed acupuncturists as a component in formulas used to treat
Rain tree nutrition: Tropical plant database: “Bandages soaked in a leaf and stem infusion were used in early American medicine to stop the bleeding of wounds; an account of this use was recorded by Dr. Francis P. Procher, a surgeon and physician in the Southern Confederacy during the Civil War. Nettle leaves were also recommended as a nutritious food and as a weight loss aid by the famous American plant forager and naturalist, Euell Gibbons.
In Brazilian herbal medicine the entire plant has been used for excessive menstrual bleeding, diarrhoea, diabetes, urinary disorders and respiratory problems including allergies. Externally, an infusion has been used for skin problems. In Peru nettle has been used against a variety of complaints such as muscular and arthritis pain, eczema, ulcers, asthma, diabetes, intestinal inflammation, nosebleeds and rheumatism. Externally it has been used for inflammations, sciatica, wounds and head lice.
In the United States many remarkable healing properties have been attributed to nettle and the leaf has been utilized for different conditions than the root. The leaves have been used as a diuretic, for arthritis, prostatitis, rheumatism, rheumatoid arthritis, high blood pressure and allergic rhinitis.”
Urtica dioica is one of the most commonly used herbal drugs in Turkey and in Jordan (Kültür S 2007, Gözüm S et al 2007 and Otoom SA et al 2006)
Complementary alternative treatments
Gözüm et al, 2003: were interested in rapidly growing
1.3. Type of tradition, where relevant
European tradition. Nettle leaf has also been used in Africa, India, Jordan, North America and Turkey.
1.4. Evidence regarding the indication/traditional use
Four different areas of indication are mentioned in the literature on nettle leaves
“Adjuvant treatment of rheumatic conditions.” (ESCOP 1997)
“Adjuvant in the symptomatic treatment of arthritis, arthroses and /or rheumatic condition. (ESCOP 2003)
“Externally: Adjuvant treatment of rheumatic conditions.” (Fintelmann V et al, Phytotherapy Manual 1989)
“When taken internally and used externally: only supportive treatment for rheumatic ailments” (Blumenthal M et al 1998, Wichtl M, 2004)
“To increase of the amount of urine and for supportive treatment of complaints associated with urination.” (DAB
“Irrigation in inflammatory conditions of the lower urinary tract.” (ESCOP 1997)
“As a diuretic, for example to enhance renal elimination of water in inflammatory complaints of the lower urinary tract.“ (ESCOP 2003)
“As irrigation therapy for inflammatory diseases of the lower urinary tract and in the prevention and treatment of kidney gravel.” (Blumenthal M et al, 1998, Wichtl M, 2004)
“As styptic in haemorrhage of the lungs, in haemorrhoids, in heavy menstrual bleeding.” (Lutomsky J and Speichert H, 1983)
“for skin complaints, including eczema and skin eruptions” (Lutomsky J et al, 1983)
From the above mentioned indications, only indication 1 and 2 can be supported as traditional indications and have to be modified according to the requirements of traditional herbal medicinal products.
Indication 1: “Traditional herbal medicinal product for relief of minor articular pain.”
Indication 2: “Traditional herbal medicinal product to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints.”
Indication 3 and 4 are reported in the literature. However, there are no products on the market supporting thirty years of traditional use with these indications.
1.5. Evidence regarding the specified posology
Preparation of the
“Pour one cup of hot water over 2 teaspoonfuls (approximately 2 g) nettle leaves. Steep for about 10 minutes and then pass through a tea strainer.” (Fintelmann V et al, Phytotherapy Manual 1989)
“4 g of nettle leaves for tea preparation three or four times daily” (DAB
0.77 g extract (7:1) twice daily (ESCOP 1997)
Ethanolic extracts corresponding to
dry extract from Urticae folium
dry extract from Urticae folium
dry extract from Urticae folium
2 hard capsules containing 268 mg dry extract each (equivalent to 2 times 4824 mg drug, product on the German market since at least 1976)
Accepted posology in the Monograph
The daily dosage is equivalent to
a)Comminuted herbal substance:
b)Liquid extract (1:5):
Pour one cup of boiling water over
h)750 mg dry extract from Urticae folium
i)450 mg dry extract from Urticae folium
j)536 mg dry extract from Urticae folium
Tincture/Spiritus (1:10): put one drop onto the aching part of the body and gently rub it. (Fintelmann V et al, Phytotherapy Manual 1989)
Fresh nettle leaf applied to the skin in the area of pain for 30 seconds once daily (ESCOP 2003).
Rapporteur’s comment: It was decided that external application forms were not suitable for consideration in the traditional use part of the monograph. The plausibility of the application of one drop of the tincture is not well justified. Usage of fresh nettle leaves is not convertible to a herbal preparation for herbal medicinal products to be marketed.
1.6. Evidence regarding the route of administration
Nettle leaf has been used internally and as well as externally (ESCOP 2003, Blumenthal M et al 1998, Fintelmann V et al, 1989)
1.7. Evidence regarding the duration of use
Four or six weeks, as a cure. (Hagers Handbuch 1998, page 723)
At the meeting in January 2008 the MLWP decided:
For indication a) 4 weeks (see Salix monograph EMEA/HMPC/295338/2007)
For indication b)
1.8. Assessor’s overall conclusion on the traditional medicinal use
Nettle leaf has been in medical use for a period of at least 30 years as requested by Directive 2004/24/EC for qualification as a traditional herbal medicinal product.
2.1.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
(e.g. primary pharmacodynamics, secondary pharmacodynamics, safety pharmacology, pharmacodynamic interactions)
Principal components of the herbal substance
Lutomsky J and Speichert , 1983: Chlorophyll
Minerals: 17.87% ash. It contains. 2.44% K2O, 5.9% CaO, 0.69% MgO, 0.68% P2O5, 2.16% SiO2, 0.83% SO3 095% Cl.
Szentmihályi K et al, 1998: Potassium sodium ratio has been determined as 63:1 in the medicinal plant and 448:1 in medicinal plant drug decoction.
Fijalek Z et al, 2003: As, Ca, Cd, Cu, Fe, Mg, Mn, Pb and Zn were determined by
Lozak A et al, 2002: The following macro- and microelements were determined in the leaf of peppermint (Mentha piperitae folium) and nettle (Urticae folium) (as tea bags) and in their infusions: As, Ba, Ca, Cd, Co, Cr, Cu, Fe, I, Li, Mg, Mn, Ni, Pb, Se, Sn, Sr, Ti, V and Zn. The determinations were performed using inductively coupled plasma mass spectrometry
In vitro studies
Obertreis B et al, 1996a:
in this test system. Calculating the content in the IDS 23 caffeic malic acid was possible but not the only active ingredient of the plant extract. Calculating the content in IDS 23 caffeic malic acid was possible but not the only active ingredients of the plant extract in the tested assay systems. It was demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23.
Obertreis B et al, 1996b: The same extract of Urtica dioica folium (IDS 23,
concentration the inhibition reached 50.5 (day 0) to 79.5% (day 21) for
Riehemann K et al, 1999: Activation of transcription factor NF (nuclear
Klingelhoefer S et al, 1999: In a whole blood culture system the nettle extract IDS 23 (Rheuma- Hek) inhibited lipopolysaccharide stimulated monocyte cytokine expression, indicating an immunomodulating effect. The immunomodulating effects of IDS 23 on phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) were investigated in vitro. METHODS: Using commercial immunoassays the distinct cytokine patterns of Th1 and Th2 cells were determined. Interleukin 2
CONCLUSION by the authors: The results suggested the effective ingredient of IDS 23 might act by mediating a switch in T helper cell derived cytokine patterns. IDS 23 might inhibit the inflammatory cascade in autoimmune diseases like rheumatoid arthritis.
Broer J and Brehnke B, 2002: The
CONCLUSION by the authors: These in vitro results showed the suppressive effect of IDS 30 on the maturation of human myeloid dendritic cells, leading to reduced induction of primary T cell responses. This might contribute to the therapeutic effect of IDS 30 on T cell mediated inflammatory diseases like RA.
Galelli A et al, 1995: Urtica dioica agglutinin (UDA) has been shown a super antigen that, in vitro, binds to specific carbohydrate structures on class II and induces a six fold enrichment of V beta 8.3+ BALB/c mice splenic T cells. Super antigens have pleiotropic effects in vivo, causing the activation, proliferation and deletion of specific T cells, but are heterogeneous in regard to their effects on T cell tolerization. Therefore, the responses of peripheral T cells from adult BALB/c mice were compared with the i.v. injection of 50 mg UDA or the bacterial super antigen staphylococcal enterotoxin B (SEB) that also recognizes the V beta 8.3 gene product. The data from this study indicated that activation, clonal expansion, anergy and death of V beta 8.3+ T cells occurred sequentially after UDA administration. Two days after UDA injection, the proportion of V beta 8.3+ T cells in the periphery was elevated to approximately twice that of normal mice. This expansion occurred in both CD4+ and CD8+ subsets. V beta 8.3+ T cells from
Inhibition of platelet aggregation
El Haouari M et al, 2006: The effects of different extracts of Urtica dioica leaves on platelet aggregation were investigated. Rat platelets were prepared and incubated in vitro with different concentrations of the tested extracts and aggregation was induced by different agonists including thrombin (0.5 U/ml), ADP (10 microm), epinephrine (100 microm) and collagen (5 mg/ml). The crude aqueous extract inhibited
At 1 mg/ml, the percent inhibition was 17.1 +/- 4.2%. Soxhlet extraction of the plant leaves with different successive solvents showed that the ethyl acetate extract exhibited the most
0.25 +/- 0.05 and 0.40 +/- 0.04 mg/ml for genins and heterosidic flavonoids, respectively. Flavonoids also markedly inhibited platelet aggregation induced by ADP, collagen and epinephrine. It is concluded that Urtica dioica has an antiplatelet action in which flavonoids are mainly implicated. These results support the traditional use of Urtica dioica in the treatment and/or prevention of cardiovascular disease.
Influence on insulin secretion
Farzami B et al, 2003: In this report, a perifusion system was arranged in which an exact number of Langerhans Islets were exposed to several fractions of a water extract (5:1) of Urtica dioica obtained by thin layer cromatography. . The active ingredient fraction caused a marked increase in insulin secretion. The highest insulin level was obtained at 60 min after the initial time of perfusion. The process was shown to be concentration dependent.
Inhibition of the protease activity
Gul N et al, 2004: The inhibitory effect of stinging nettle leaf extract on the protease activity of botulinum neurotoxin type A and B light chains was investigated. The nettle leaf infusion was fractionated and
demonstrated that a
Inhibition on adenosine deaminase activity
Durak I et al, 2004: Aqueous extract of Urtica dioica showed significant inhibition on adenosine deaminase activity in prostate tissue from patients with prostate cancer. Possible effects of aqueous extract of Urtica dioica leaves on adenosine deaminase activity in prostate tissue from patients with prostate cancer were investigated. METHODS: Ten prostate tissues from patients with pathologically proven localized prostate cancer (Gleason scores 4 to 7) were used in the study. In the tissues, ADA activities with and without preincubation with different amounts of Urtica dioica extracts were performed. RESULTS: Aqueous extract of Urtica dioica showed significant inhibition on adenosine deaminase (ADA) activity of prostate tissue.
CONCLUSION by the authors: ADA inhibition by Urtica dioica extract might be one of the mechanisms in the observed beneficial effect of Urtica dioica in prostate cancer.
In vivo studies
Farzami B et al, 2003: A water extract of Urticae dioica leaves was purified by using TLC with several changes of solvent to obtain fractions for further in vivo studies. A solvent mixture of 30/70% water/isopropanol was found most suitable for initial separation. Fraction F1 was found to increase the insulin content of blood sera in normal and streptozotocin diabetic rats that were injected intraperitoneally (i.p.). The in vivo studies showed that not only an increase in insulin level of blood sera was observed in rats after 30 min from the initial point of injection but a simultaneous decrease of blood sugar was detected when similar sera were tested for glucose. The increase in insulin level was 6 times during 120 min. The decrease in blood sugar was found to be similar both in the level and time of initiation. The authors assumed that F(1) was the active ingredient of plant leaves extract. The results showed that the blood lowering effect of the extract was due to the enhancement of insulin secretion by Langerhans Islets.
Rapporteur’s comment: The results of this study can not be considered to be relevant for the traditionally applied doses and preparations.
Uterine muscle activity
The effect of extracts of Urtica dioica leaves on mouse gravid and
Rapporteur’s comment: This article is not taken into consideration because it is on Nettle herb.
Schoening, 1996: Extract IDS23 (solvent 50% ethanol, 25,100 and 300 mg/kg) produced a dose dependent
a significantly lower lymphocyte infiltration compared to control (p<0.05). The effect was similar to diclofenac.
Konrad A et al, 2005: The stinging nettle leaf extract, IDS 30, has been used as an adjuvant remedy in rheumatic diseases dependent on a cytokine suppressive effect. The authors investigated the effect of IDS 30 on disease activity of murine colitis in different models. METHODS:
CONCLUSIONS by the authors: The
Özen and Korkmaz, 2003: The effects of two doses (50 and 100 mg/kg body weight given orally for 14 days) of an ethanolic (80% V/V) extract of Urtica dioica L. leaf and butylated hydroxyanisole (BHA) were investigated, for phase I and phase II enzymes, antioxidant enzymes, lactate dehydrogenase, lipid peroxidation and sulfhydryl groups in the liver of Swiss albino mice
Toldy A et al, 2005: The effects of exercise and nettle supplementation on oxidative stress markers in the rat brain were investigated. Chronic swimming training and phytotherapeutic supplementation have been assumed to alleviate oxidative damage and to support cell survival in the brain. The effect of forced, chronic swimming training, and enriched lab chow containing 1% (W/W) dried nettle (Urtica dioica) leaf were investigated for oxidative stress, inflammation and neurotrophic markers in Wistar rat brains. The rats were divided into groups subjected to swimming training (6 weeks) or to nettle supplementation (8 weeks) or to a combination of these two treatments. The level of oxidative stress was measured by electron spin resonance (EPR), and by the concentration of carbonylated proteins. Nettle supplementation resulted in a decreased concentration of free radicals in both cerebellum and frontal lobe. Swimming, however, did not influence significantly the oxidative damage nor was it
reflected in the carbonyl content. The protein content of nerve growth factor (NGF), and
Cetnius E et al, 2005: The potential role of Urtica dioica (UD) (Urticaceae) plant for prevention of oxidative stress in muscle tissues generated by tourniquet application in rats was investigated. Wistar rats were used in this study. The UD extract or 1.15% KCl aqueous solution, in which UD leaf samples (2 g of leaf was homogenized in 10 ml of 1.15% KCl ) were homogenized, was given to each group of eight rats once a day for 5 days through an intraesophageal canule. No treatment was applied to untreated group. Tourniquets were applied to the left posterior limb of rats for 1 or 2 h followed by a reperfusion period of 1 h. After the ischemia and reperfusion, the rats were killed with a high dose of anesthetic drug, and malonyldialdehyde (MDA) levels were measured in their tibialis anterior muscles. Basal MDA levels were obtained from tibialis anterior muscles of 8 control rats, which were not exposed to ischemia. MDA levels were lower in the
2.1.2. Assessor’s overall conclusions on pharmacology
The same extract of Urtica dioica folium significantly and
The treatment of different cells with this extract potently inhibited
Mice with chronic DSS colitis or
In an in vitro study a
In vitro results showed the suppressive effect of
Thus the traditional use of nettle leaves for treatment of minor rheumatic disorders is plausible. There are no studies addressing possible diuretic effects of nettle leaf. Unfortunately it can not be found any study which investigates the diuretic effect of nettle leaf, but only for nettle herb. Because of the similarity of nettle herb and nettle leaf data existing for nettle herb may also be considered to support the traditional use of nettle leaf in this therapeutic area.
2.2.1. Overview of available data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
(e.g. absorption, distribution, metabolism, elimination, pharmacokinetic interactions with other medicinal products)
There is no pharmacokinetic study with nettle leaf.
2.2.2. Assessor’s overall conclusions on pharmacokinetics
2.3.1. Overview of available data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
(e.g. single/repeat dose toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicity, local tolerance, other special studies)
Turker Au and Usta C, 2008: Screening of antibacterial activity and toxicity of 22 aqueous plant extracts from 17 Turkish plants was conducted. Antibacterial activity was performed with six bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes,
Staphylococcus aureus and Staphylococcus epidermidis. Extracts of Tussilago farfara leaves, Helichyrsum plicatum flowers, Solanum dulcamara aerial parts and Urtica dioica leaves gave the best inhibitory activity against Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis. Of the 22 plant extracts, 20 extracts displayed toxicity (LC(50) was <1000 mg/l) in the brine shrimp bioassay. For radish seed bioassay, two different determinations (root length and seed germination) were performed with a comparison between two concentrations (50,000 mg/l) and 10,000 mg/l). At low concentration (10,000 mg/l), Solanum dulcamara aerial parts and Primula vulgaris leaf extracts were observed to inhibit the root length more than the other plant extracts. Also, the most inhibitive plant extract for seed germination was obtained with Solanum dulcamara aerial parts.
Özen and Korkmaz, 2003: Two doses (50 and 100 mg/kg body weight) of an
2.3.2. Assessor’s overall conclusions on toxicology
Specific data on the toxicology of nettle leaf are limited.
3. CLINICAL DATA
3.1. Clinical Pharmacology
184.108.40.206. Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
There are no relevant data.
220.127.116.11. Assessor’s overall conclusions on pharmacodynamics
There are no relevant data.
18.104.22.168. Overview of available data regarding the herbal substance(s)/herbal preparation(s) including data on constituents with known therapeutic activity.
There are no relevant data.
22.214.171.124. Assessor’s overall conclusions on pharmacokinetics
There are no relevant data.
3.2. Clinical Efficacy
3.2.1. Dose response studies
There are no studies available.
3.2.2. Clinical studies (case studies and clinical trials)
Extracts of Nettle leaf were studied in osteoarthritis.
According to the Points to consider on clinical investigation of medicinal products used in the treatment of osteoarthritis (CPMP/EWP/784/97) osteoarthritis is a disorder which can potentially affect all synovial joints. It is characterised by degradation and regeneration of articular cartilage and bone. The pathological changes can be focal or more generalized and these changes often correlate poorly with clinical symptoms and signs. However, it has been suggested that asymptomatic osteoarthritis, diagnosed radiologically, is a precursor of symptomatic disease. Osteoarthritis, particularly of the large joints of lower limbs – for example, knees and hips – is now widely recognized as a major cause of the chronic disability in the population.
Medication for osteoarthritis may affect symptoms and/or modify structures. Three classes of drugs act in osteoarthritis:
Five open, multicentric, post marketing surveillance studies have been carried out on patients with arthritic or rheumatic complaints using a preparation containing a dry
Ramm S and Hansen C, 1995: An extract preparation was tested in a multicentric
152 (79.6%) were
Hansen C, 1996 and Sommer
Ramm S and Hansen C, 1996: The results of a 3 week post marketing surveillance study in 1528 patients (1392 arthrose, 268 rheumatoid arthritis) showed that the herbal medicinal product Rheuma- Hek (335 mg/capsule IDS 23 2 times 2 capsules) was very well tolerated and effective in alleviating rheumatic complaints. The dose of the existing treatment with NSAIDs given in parallel with IDS 23 could be reduced in 42.8% of the patients and could be stopped in additional 19.75 % of the patients.
Ramm S and Hansen C, 1997: The previously mentioned Urticae folium extract was tested in an open, multicentric clinical trial. The patient number was 8955, and they suffered from osteoarthrosis or rheumatoid arthritis. The patients took 2 times 2 capsules nettle leaf extract (335 mg/caps. IDS 23, Rheuma- Hek) for three weeks. About half of the patients (49.5%) were
Results: 2754 patients (64%) could markedly reduce the dose of the parallel NSAID. 26.2% of the patients could stop treatment with NSAID, and further 37.8% of the patients could reduce the dose of them about by 50%. NSAID therapy did not change in 28.4% of the cases and only 7.6% of the patients needed NSAID parallel to
Wolf F, 1998: The
The efficacy of the product was evaluated with the help of a gonarthrose specific patient questionnaire. There were 5 questions about pain on the joints (warmth, swelling, sensitivity to pressure, redness), 2 question about rigidity of the joints and 17 questions about function of the joint. It was also investigated how the product influenced the process of the illness (frequency and duration of painful schubs).
Under continuous therapy with
As IDS 23 was shown to reduce formation of cytokinin
Open studies with other preparations
Wolf F et al, 2001: In an observational study the clinical effectiveness of an extract of nettle leaf (145 mg dry extract of nettle leaves
42%. Joint- function was evaluated with the help of
Randall C et al, 1999: An exploratory study was carried out on the alleviation of pain by external application of fresh nettle leaves, which causes urtication. From analysis of recorded
Chrubasik S et al, 1997: Forty individuals suffering from an acute attack of chronic joint disease (acute arthritis) took part in an open randomised study comparing the effects of 50 mg diclofenac and 50 g of a prepacked stewed nettle leaf purée (Urtica dioica L., water content 95.5%, caffeoyl malic acid content 20 mg, patient’s number=19) with 2 times 100 mg diclofenac (n=17). Both groups also received the gastro protective prostaglandin analogue misoprostol. The assessment was based on the decrease of the elevated
Rapporteur’s comment: This article is not considered because it is assumed that it is about nettle herb.
Randall C et al, 2000: A randomized controlled
27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. Patients were instructed how to cut a leaf (with hand in plastic bag) and apply the lower surface to the painful area of thumb or index finger base with gentle pressure for about 30 seconds, moving the leaf twice. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a
distressing. 1 patient had a persistent rash on her forearms after treatment but this had occurred before and was not necessarily due to stinging nettle. The stinging nettle treatment caused a rash on the hand of one patient who discontinued treatment because he needed heavy gloves for his job. The result of this trial demonstrated an analgesic effect and reduction of disability after one week treatment with stinging nettle. A weakness of the design was that the “blinding” of both doctor and patients was incomplete; one patient reported stinging and rash with the application of one plant treatment. Patients were not, however, given to understand that any benefit might be associated with the sting, and the patients did not seem to make this assumption. The sample size was small, but crossover of treatment considerably increased the power of the results. Patients’ compliance was high.
3.2.3. Clinical studies in special populations (e.g. elderly and children)
There is no study available.
3.2.4. Assessor’s overall conclusions on clinical efficacy
The quality of above mentioned clinical studies with nettle leaf in osteoarthritis is poor, not convincing. They all show a trend of effectiveness in the domains investigated, which needs, however, to be proven in confirmatory studies. They do not fulfil the requirements of the above mentioned CHMP guideline.
3.3. Clinical Safety/Pharmacovigilance
The stinging nettle (Urtica dioica) is a common weed that can cause a wide range of cutaneous reactions. Contact with the hairs or spines on the stems and leaves of the stinging nettle causes the release of several biologically active substances. The released chemicals act to cause itching, dermatitis, and urticaria within moments of contact. (Anderson BE et al, 2003)
Mild gastrointestinal complaints (e.g. nausea, vomiting and diarrhoea) and allergic reactions (e.g. itching, exanthema and hives) may occur. The frequency is not known. (Data resulting from market overview)
In clinical studies
Only 1.2% of the patients experienced adverse effects, mainly
No serious adverse effects were reported from 5 clinical studies in which in total 10,368 patients took 2 times 670 mg of a dry
Spontaneous case reports for the
Allergy, dry skin, Urticaria, pruritus, rash erythematous, rush postular, dyspepsia, nausea, faecal incontinence, diarrhoea, sleep disorders, dizziness.
3.3.3. Serious adverse events and deaths
3.3.4. Laboratory findings
No data available.
3.3.5. Safety in special populations and situations
No data available.
126.96.36.199. Intrinsic (including elderly and children) /extrinsic factors
No data available.
188.8.131.52. Contra indications (hypersensitivity and allergic potential to be both covered)
ESCOP: None known.
Blumenthal M et al, 1998; Wichtl M, 2004: None known.
Note: No irrigation therapy in cases of oedema due to impaired cardiac or renal function.
Hagers Handbuch: Water retention (oedema) as a results as a result of impaired cardiac and renal function.
Tropical Plant database
Nettle has been documented in animal studies to lower blood pressure and heart rate. Those with heart conditions should seek the advice and supervision of a health practitioner to determine if nettle is suitable for their condition and monitor its effects.
Nettle has been documented to have diuretic effects. Chronic use of this plant may be contraindicated in various medical conditions where diuretics are not advised. Chronic
Contraindications in the Monograph
Hypersensitivity to nettle herb.
Condition where a reduced fluid intake is recommended (e.g. severe cardiac or renal disease).
Blumenthal M et al, 1998; Hagers Handbuch 1998; Wichtl M, 2004
In irrigation therapy, care must be taken to ensure an abundant fluid intake.
Excessive use may influence the treatment of hypertension and diabetes.
Rapporteur’s comment: There are no data (clinical or preclinical) which support this statement.
Articular pain accompanied by swelling of joint, redness or fever should be examined by a doctor.
The use is not recommended in children under 12 years of age because of the lack of available experience.
If minor urinary tract complaints worsen and symptoms such as fever, dysuria, spasm, or blood in the urine occur during the use of medicinal product, a doctor or a qualified health care professional should be consulted.
184.108.40.206. Drug interactions
None reported. (ESCOP 1997, 2003; Blumenthal M et al, 1998)
Due to the content of vitamin K in nettle leaf the herbal substance or preparations thereof could attenuate the efficacy of anticoagulants like phenprocumon or warfarin (labelling applied by the German authority). According to data provided during public consultation, the Vitamin K content described in the literature is
Because there have been no reports on clinically observed drug interactions with nettle leaf it was decided to introduce the wording “none reported” into the monograph.
220.127.116.11. Use in pregnancy and lactation
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 case of overdose has been reported.
18.104.22.168. Drug abuse
No data available.
22.214.171.124. Withdrawal and rebound
No data available.
126.96.36.199. 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.
3.3.6. Assessor’s overall conclusions on clinical safety
Nettle leaf preparations are
4. ASSESSOR’S OVERALL CONCLUSIONS
The traditional use of nettle leaf in minor articular pain is supported by pharmacological data, as IDS 23 hinders the building of cytokinin