Stinging Nettle Root, Studies
Aromatase Inhibitors from *Urtica dioica* Roots
Understanding the pathological manifestations of Aromatase Excess Syndrome: Lessons for clinical diagnosis (Expert Review of Endocrinology and Metabolism).
Search for the antiprostatic principle of stinging nettle (Urtica dioica) roots
Urtica dioica agglutinin. A superantigenic lectin from stinging nettle rhizome.
Carbohydrate binding properties of the stinging nettle (*Urtica dioica*) rhizome lectin
Clinical pharmacology
Benign prostatic hyperplasia
Placebo-controlled clinical trials
Three double-blind, placebo-controlled clinical trials have assessed the efficacy of oral administration of Stinging Nettle root for the symptomatic treatment of lower urinary tract disorders resulting from BPH . One study assessed the efficacy of a 20% methanol extract of the roots in 50 men with BPH stages I and II . A significant increase in urine volume (by 43.7%; P = 0.027) and a significant decrease in serum levels of SHBG (P = 0.0005) was observed in patients treated with 600mg extract daily for 9 weeks. A modest increase in maximum urinary flow of 8% was also observed in the treated group; however, it was not significant. Another study assessed the efficacy of a 20% methanol extract in 40 men with BPH. Treatment with 1200mg extract daily for 6 weeks decreased the frequency of micturition and serum levels of SHBG. The third study assessed the efficacy of a methanol extract in the treatment of 32 men with BPH stage I. A 4–14% increase in average urinary flow and a 40–53% decrease in postvoid residual volume were observed in patients treated with 600 mg extract daily for 4–6 weeks.
Clinical trials without controls
Numerous clinical trials without controls have assessed the efficacy of oral administration of various Stinging Nettle root extracts (20% methanol or 30–45% ethanol) for the symptomatic treatment of lower urinary tract disorders (nocturia, polyuria, dysuria, urine retention) resulting from BPH . One trial assessed the efficacy of a 40% ethanol extract of the roots in 67 men with BPH. Treatment with 5ml daily for 6 months decreased nocturia and postvoid residual volume, but did not reduce prostate enlargement . In another trial, a 20% methanol extract of the roots was assessed in 89 men with BPH. Treatment with 600mg daily decreased the postvoid residual volume in 75% of patients after 3–24 months. In a study of 26 men with BPH stage I or II, a decrease in prostate volume was observed in
54% of patients, and a decrease in postvoid residual volume was observed in 75% of patients, after treatment with 1200mg methanol extract daily for 3–24 weeks. Ten men with BPH were treated with 30–150 drops of a 45% ethanol extract of the root daily for 30 days. After treatment, the postvoid residual volume decreased by 66%. In a study of 39 men with BPH stages I–III, an improvement in urinary flow, and a reduction in postvoid residual volume, nocturia and polyuria were seen in 95% of patients after 6 months of treatment with a 20% methanol extract (600–1200mg daily). Twenty-seven men with BPH stages I and II were treated with a 20% methanol extract of the roots for 3.5 months. Postvoid residual volume decreased significantly in 75% of patients (P < 0.001), and maximum urinary flow increased significantly in 50% of patients (P < 0.002).
Three large-scale multicentre studies involving 14033 men with BPH assessed the efficacy of a 20% methanol extract . In one study, a decrease in nocturia and polyuria was seen in 91% of patients after 6 months of treatment. In another study, a 50% decrease in nocturia was observed in patients treated with 1200mg extract daily for 10 weeks. In the third study, significant improvements in both urinary flow and postvoid residual volume were observed in 4480 patients treated with 600–1200mg extract daily for 20 weeks (P < 0.01)
Effects on prostate morphology
Three studies without controls examined the effect of various methanol extracts of Stinging Nettle root on prostate morphology. Prostate cells were obtained from patients with BPH by needle biopsy, and were analyzed for morphological changes before and after treatment. In two of the studies, cells were taken from the patients at various intervals during treatment . In the third study, cells were obtained once from the patients, and treatment with the extract was carried out in vitro. In the first study, 31 men with BPH stages I and II were treated orally with 1200mg of a 20% methanol root extract daily for 20 weeks. Prostate cells were analyzed every 4 weeks by fluorescent microscopy. After 4–16 weeks of treatment, an increase in nuclear volume, as well as hydropic swelling and vacuolization of the cytoplasm, were observed. In the second study, prostate cells from four men with BPH stage I were examined by electron microscopy. After 6 months of oral treatment with a 20% methanol extract (1200mg daily), a reduction in the activity of smooth muscle cells and an increase in the secretory activity of glandular epithelial cells were observed . In the third study, prostate glandular epithelial cells from 33 patients with BPH were analyzed by fluorescent microscopy following incubation of the cells in vitro with a 20% methanol extract of the root. Treatment with the extract caused an increase in nuclear volume, loosening of chromatin and hydropic swelling of the cytoplasm. In addition, the number of
homogeneous secretory granules was reduced, indicating a reduction in the biological activity of these cells.
Experimental pharmacology
Anti-inflammatory activity
An ethanol extract of Radix Urticae inhibited the activity of human leukocyte elastase and reduced the amount of the enzyme released by activated polymorphonuclear granulocytes during the inflammatory response. The extract also inhibited degradation of a peptide substrate in vitro by human leukocyte elastase (IC50 3.6mg/ml) and bovine elastin (IC50 68mg/ml) . Intragastric administration of a polysaccharide fraction isolated from Radix Urticae to rats (40mg/kg body weight) suppressed carrageenan-induced footpad edema for up to 20h . The activity of the polysaccharides was comparable to that of indometacin (10mg/kg body weight).
Lymphocyte proliferation
A lyophilized aqueous extract (10mg/ml) and a 40% alcohol extract of the roots (100mg/ml) stimulated human lymphocyte proliferation in vitro by 63% and 100%, respectively. Polysaccharides isolated from an aqueous root extract induced human lymphocyte proliferation in vitro (10–100mg/ml). An ethyl acetate extract of the roots induced cell differentiation in human promyelocytic leukaemia HL-60 cells in vitro (ED50 4mg/ml). Urtica dioica agglutinin (500ng/ml), however, inhibited lymphocyte proliferation and the binding of epidermal growth factor to its receptor on A431 epidermoid cancer cells in vitro. The lectin also exhibited immunomodulatory effects on T-lymphocytes in a dose-dependent manner). Urtica dioica agglutinin bound to the cell membrane of prostatic hyperplastic cells and inhibited
their proliferation.
Effect on benign prostatic hyperplasia
Effect on sex hormone-binding globulin
Sex hormone-binding globulin (SHBG) is a blood plasma protein that binds to circulating androgens and estrogens, thereby regulating their free concentration in plasma. The plasma membrane of the human prostate contains specific SHBG receptors, and SHBG appears to play a role in the development of BPH. A 10% hydroalcoholic extract of the root reduced the binding capacity of SHBG (isolated from human plasma) for 5a-dihydrotestosterone by 67% in vitro .
An aqueous extract of the root (0.6–10.0mg/ml) inhibited the binding of 125I-labelled SHBG to human prostate membranes in vitro . The lignan, secoisolariciresinol, and a mixture of the isomeric compounds 13-hydroxy-9-cis,11-trans-octadecadienoic acid and 9-hydroxy-10-trans,12-cis-octadecadienoic acid isolated from a methanol root extract, reduced the binding of SHBG to 5a-dihydrotestosterone. Secoisolariciresinol and its main intestinal transformation products, (-)-3,4-divanillyltetrahydrofuran and enterofuran, displaced the binding of 5a-dihydrotestosterone to SHBG in vitro by 60%, 95% and 73%,respectively.
Enzymatic activity
Intragastric administration of a 30% ethanol extract of the root to male mice inhibited the activities of 5a-reductase and aromatase (ED50 14.7 and 3.58mg/ml, respectively) . However, a hydroalcoholic extract of the root dissolved in dimethyl sulfoxide did not inhibit the activity of 5a-reductase from human prostate cells in vitro (up to 500mg/ml) . A standardized hydroalcoholic extract of the roots (IC50 338mg/ml) inhibited aromatase activity in vitro.
A heptane-soluble fraction of the extract was the most effective inhibitor (IC50 9mg/ml) . Both ursolic acid and 14-octacosanol isolated from a methanol extract of the roots inhibited the activity of aromatase in vitro . 9-Hydroxy-10-trans,12-cis-octadecadienoic acid isolated from the roots inhibited the activity of aromatase in vitro. Butanol, ether, ethyl acetate and hexane extracts of the roots inhibited the activity of sodium- and potassium-adenosine triphosphatase isolated from prostatic hyperplastic cells by 27.6–81.5%. In addition, steroidal components of the roots, stigmast-4-en-3-one, stigmasterol and campesterol (1mmol/l to 1mmol/l), inhibited sodium- and potassium-adenosine
triphosphatase activity by 23–67%.
Effect on prostate growth
Intragastric administration of a hexane extract of the roots (1.28 g daily) to castrated rats did not inhibit prostate growth stimulated by testosterone or dihydrotestosterone. Intraperitoneal administration of a hydroalcoholic extract of the roots (20mg/kg body weight) suppressed testosterone-stimulated increases in prostate weight and prostatic ornithine decarboxylase activity in castrated rats . Daily oral administration of a hydroalcoholic extract of the root to dogs with BPH (30mg/kg body weight) decreased prostate volume by 30% after 100 days of treatment..
The effect of various root extracts was assessed after implantation of the fetal urogenital sinus into the prostate gland of adult mice. Intragastric administration of a butanol, cyclohexane or ethyl acetate extract of the root (0.25ml/daily for 3 weeks) had no effect on the development of BPH in mice. However, intragastric administration of the same dose of a 20% methanol extract of the root reduced the development of BPH by 51.4%.