Coherence 1/99



S. Chrubasik, MD, PhD and P. Shvartzman, MD, PhD *

* From the Department of Family Medicine, Ben-Gurion University of the Negev, POBox 653, Beer-Sheva 84105, Israel



Extracts of Urtica dioica leaves are used for the treatment of rheumatic pain. The main active principles act via the inhibition of the eicosanoid biosynthesis, the cycloxygenase as well as the lipoxygenase pathway. Furthermore, cytokine release is inhibited. A post-marketing surveillance in almost 9000 patients proves the good compatibility of Urtica dioica leave extract IDS 23 and gives evidence that treatment with NSAIDs can be reduced. About 1 % of the patients suffered from side-effects. There is evidence that daily consumption of stewed Herba Urtica dioica stew 50 g/day potentiates the NSAID antiphlogistic effect of 50 mg diclofenac in patients suffering from acute arthritis. C-reactive protein and clinical symptoms decreased by up to 70 %. This effect was similar to that of diclofenac 200 mg/day.

Key words: rheumatic pain, phytotherapy, urtica


Standardized stinging nettle extracts are used to prepare medications. The plant (Fig. 1) grows in Europe, including the Alps (up to 2500 m) and some parts of Asia and North America. The drug, dried herba or folium Urticae dioicae, contains more than one active principle with antirheumatic activity, among them flavonoids, caffeoylmalic acid, and unknown cytokine release-inhibiting substances (1). Fresh or dried material may also be used, provided it complies with the Deutsches Arzneibuch or the Pharmacopea Helvetica.

Fig. 1 Stinging Nettle

For adjuvant treatment of rheumatic conditions, the ESCOP Monograph (1) recommends for adults up to 15 g of the drug (tea of 5 g crude drug 3 times daily). Alternatively, 0.77 g extract (7:1) may be used twice daily or tincture 1:5 (25% ethanol) 6-18 ml per day or 30-45 ml of fresh juice.

The quantity of caffeoylmalic acid in stinging nettle preparations depends not only on the origin of the plant and its part investigated (highest concentrations are found in the leaves), but also on the choice of the extraction solvent and the extraction method (2). Teas and preparations of fresh plants may provide more caffeoylmalic acid than oral medications (Fig. 2). Although caffeoylmalic acid is one of the active principles in preparations from stinging nettle, the clinical efficacy of stinging nettle preparations is not correlated with their caffeoylmalic acid content. Thus, other effective ingredients must be present and need, thus, to be evaluated for standardization in terms of quality of the preparation and daily dosage (3).

Fig. 2 Caffeoylmalic acid content of various Urtica preparations (2)



Extractum Urticae dioicae folium and the main phenolic ingredient of caffeoylmalic acid inhibit the biosynthesis of cyclooxygenase derived reactions (IC50 extract IDS-23 92 g/ml, caffeoyl malic acid 38 g/ml). Concerning the 5-lipoxygenase products, extract IDS 23 showed a partial inhibitory effect, whereas caffeoylmalic acid inhibited the leukotriene B4 synthesis in a dose-dependent manner (4). The concentrations of cytokines (tumor necrosis factor (TNF)-alpha and interleucin (IL)-1beta) after lipopolysaccharide (LPS) stimulation in whole blood from healthy volunteers (5), as well as in patients suffering from osteoarthritis (6), ex vivo in vitro were dose-dependently reduced by simultaneously giving Stinging nettle leave extract IDS-23.

In accordance with this, a significant decrease of LPS-stimulated cytokine release in whole blood from volunteers was demonstrated after oral intake of 1340 mg IDS extract over 21 days (5). In contrast, the release of interleucin-6 was stimulated by IDS-23, comparable to LPS-stimulation (7). Phenolpropanoid derivatives and flavonoids did not affect the cytokine release (7). Stinging nettle extract, prepared as 0.25 mg/ml of a lyophyilizised aqueous extract in water, produced 93% inhibition of platelet-activating factor-induced exocytosis of elastase from human neutrophiles. The same extract (0.2 mg/ml) showed no activity in a test for inhibition of the biosynthesis of prostaglandins from 14C-arachidonic acid (8). Furthermore, in the adjuvans-induced arthritis test in rats, a dose-dependent reduction of the joint circumference was achieved after 25 days of treatment with IDS-23 extract. Stinging nettle extract also has some spasmolytic activity, as demonstrated by the antagonism of the acetylcholine-induced rat ileum contractions (9) or a slight contraction followed by relaxation in isolated smooth muscle from the non-pregnant mouse (10). Application of the extracts to uterine muscle from the pregnant mouse produced a diametrically opposed effect. The authors concluded that the extracts had adrenolytic activity, similar to the action of dihydroergotamine and inhibiting the effect of adrenaline. Contradictory results were achieved when investigating the central analgesic efficacy of stinging nettle extracts (11,12). However, local application to the rat tail of 0.05 ml of stinging nettle aqueous extract (100 mg lyophilized extract/ml) in the same region as subsequent application of heat in the tail flick test, produced a local anesthetic effect comparable to that of lignocaine (11).



A post-marketing surveillance included 8955 patients suffering from osteoarthritis and rheumatoid arthritis (13). The patients received 1340 mg Urtica extract IDS-23 (Rheuma-HekR) per day over a three-week period. Pain at rest and during exercise, as well as physical impairment, was assessed on a verbal rating scale ranging from 0-4. Ratings improved by 55%, 45% amd 38%, respectively. Onset of effectiveness occurred after 11 days. In about 60 % of the patients who took NSAIDs before the beginning of treatment, NSAID consumption could be reduced or entirely eliminated. The response was higher the shorter the duration of pretreatment and the less patients had consumed NSAIDs before the beginning of the post-marketing surveillance. Adverse effects (gastrointestinal complaints, allergies, pollakiuria, pruritus, etc.) occurred in 1.2 % of the patients.

Forty individuals suffering from acute arthritis took part in an open randomized study comparing the effects of diclofenac 50 mg plus stewed stinging nettle with diclofenac 200 mg (14). Thirty-seven patients completed the study. Assessment was based on the decrease of the elevated acute phase protein CRP and the clinical signs of acute arthritis (physical impairment, subjective pain, pressure pain, and stiffness, all assessed on a verbal rating scale ranging from 0-4). Groups were clearly matched for size, weight and sex distribution, but not for age and origin of pain. C-reactive protein did not correlate with the number of affected joints. After two weeks, median scores had improved by about 70 % relative to the initial value in both groups. Only minor adverse effects occurred during treatment. Thus, stewed Herba Urticae dioicae may enhance the NSAID antirheumatic effectiveness.



According to the European Monograph, the duration of treatment with Urticae folium/herba extract is not restricted. Contraindications are not known, nor are special warnings or precautions required. In accordance with general medical practice, the extract should not be used during pregancy and lactation without medical advice. Undesirable effects are reported in about 1% of patients (13), mainly gastrointestinal and allergic adverse events. No toxic effects are reported. Preclinical safety data include the intraperitoneal LD50 of an aqueous Urtica extract in mice of 3.625 g/kg body weight (11) and a study investigating an ethanolic extract equivalent to 2 g dried drug per kg, which showed low toxicity in both rats and mice after oral and intraperitoneal administration (12).



1. ESCO Monograph, Urticae Folium/ Herba, Juli 1997, Tel. 0031-525-686101

2. Bauer R, Holz A, Chrubasik S. Kaffeoelaepfelsaeure als Leitsubstanz in Zubereitungen aus der Brennessel (Urtica dioica). In: Rheumatherapie mit Phytopharmaka. Eds. S. Chrubasik, D. Loew, Hippokrates-Verlag Stuttgart, 1997, pp 112-120

3. Chrubasik S, Bauer R. 1997 unpublished

4. Obertreis B, Giller K, Teucher Th, Behnke B, Schmitz H. Antiphlogistische Effekte von Extractum Urticae dioicae foliorum im Vergleich zu Kaffeoelaepfelsaeure. Drug Res, 1996, 46: 52-56

5. Teucher Th, Obertreis B, Ruttkowski T, Schmitz H. Zytokin-Sekretion im Vollblut-gesunder Probanden nach oraler Einnahme eines Urtica dioica L.-Blattextraktes. Drug Res, 1996, 46: 906-10

6. Obertreis B, Teucher T, Behnke B, Schmitz H. Pharmakologische Effekte des Urtica dioica-Blattextraktes IDS-23. In: Rheumatherapie mit Phytopharmaka. Eds. S. Chrubasik, D. Loew, Hippokrates-Verlag Stuttgart, 1997, pp 90-96

7. Obertreis B, Ruttkowski T, Teucher Th, Behnke B, Schmitz H. Ex-vivo-in-vitro Hemmung der Lipopolysaccharid-stimulierten Tumor-Nekrose-Faktor-alpha und Interleukin-1beta-Sekretion in humanem Vollblut durch Extractum Urticae dioicae foliorum. Drug Res, 1996, 46: 389-94

8. Tunon H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory activity of some wedish medical plants. Inhibition of prostaglandin biosynthesis and PAF-induced exocytosis. J Ethnopharmacol, 1995, 48: 61-76

9. Boegge SC, Kesper S, Verspohl EJ, Nahrstedt A. Reduction of Ach-induced contractions of rat isolated ileum by coptisine, Caffeoylmalic acid, chelidonium majus and Corydalis lutea extracts. Planta Medica, 1996, 62: 173-74

10. Broncano FJ, Rebuelta M, Lazaro-Carrasco MJ, Vivas JM. Estudio del effecto sobre musculatura lisa uterina de distintos preparados de las hojas de Urtica dioica L. An Real Acad Farm, 1987, 53: 69-76

11. Lasheras B, Turillas P. Cenarruzabeitia E. Etude pharmacologique preliminaire de Prunus spinosa L, Amelanchier ovalis Medikus, Juniperus communis L et Urtica dioica L. Plant Med Phytother, 1986, 20: 219-26

12. Tita B, Faccenddini P, Bello U, Martinioli L, Bolle P. Urtica dioica L.: Pharmacological effect of ethanol extract. Pharmacol Res, 1993, 27 (Suppl 1): 21-2

13. Ramm S, Hansen C. Brennesselblaetter-Extrakt: Wirksam und vertraeglich bei Arthrose- und rheumatoider Arthritis. In: Rheumatherapie mit Phytopharmaka. Eds. S. Chrubasik, M. Wink, Hippokrates-Verlag Stuttgart, 1997, pp 97-106

14. Chrubasik S, Enderlein W, Bauer R, Grabner W. Evidence for antirheumatic effectiveness of stewed Herba urticae dioicae in acute arthritis: a pilot study. Phytomedicine, 1997, 4: 105-108