Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia
J Urol 2000 May;163(5):1451-6
PURPOSE: We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. MATERIALS AND METHODS: We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. RESULTS: Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. CONCLUSIONS: Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.
Chronic Venous Insufficiency [Effects of horse-chestnut seed extract on transcapillary filtration in chronic venous insufficiency] (Published in German)
J Am Osteopath Assoc 2000 Feb;100(2):89-96
European physicians treat benign prostatic hyperplasia (BPH) with saw palmetto extract (SPE), while American physicians generally disregard SPE because "research is lacking." The authors investigated this discrepancy with a literature search and a clinical trial. The literature search began with MEDLINE, then expanded to "alternative" databases, including AGRICOLA, EMBASE, IBIS, and Cochrane, plus a manual search of unindexed herbal journals. The clinical trial was an experimental case study in which a 67-year-old man with symptomatic BPH was randomly administered SPE (160 mg standardized extract twice daily) or placebo. Outcome measures included the American Urological Association Symptom Index (AUASI), serum prostate-specific antigen, and prostate volume. Our expanded literature search revealed 58 clinical trials, whereas MEDLINE yielded only 19 clinical trials, or 33% of the total. Our clinical trial measured a baseline AUASI score of 20, which improved to 7 after unblinded administration of SPE. Subsequent double-blinded placebo produced a score of 14, and final single-blinded allotment of SPE produced a score of 11. Prostate-specific antigen was 10.3 ng/mL at baseline and 10.7 ng/mL at trial's conclusion. Baseline prostatic volume was 92 mL, and end volume was 75 mL. In conclusion, MEDLINE proved inadequate as a stand-alone search engine for locating information about an herbal medicine. Our experimental case study, similar to N = 1 research methodology, proved suitable for clinical evaluation of an herbal medicine in a rural private practice. SPE improved the patient's BPH. Unstandardized look-alike herbs may act as nontherapeutic placebos and may undermine consumer confidence in herbal medicine.
The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes.
Hryb DJ, Khan MS, Romas NA, Rosner W Department of Medicine, St. Luke's/Roosevelt Hospital Center, New York, N.Y. 10019. Planta Med 1995 Feb;61(1):31-2
Extracts from the roots of the stinging nettle (Urtica dioica) are used in the treatment of benign prostatic hyperplasia. The mechanisms underlying this treatment have not been elucidated. We set out to determine whether specific extracts from U. dioica had the ability to modulate the binding of sex hormone-binding globulin to its receptor on human prostatic membranes. Four substances contained in U. dioica were examined: an aqueous extract; an alcoholic extract; U. dioica agglutinin, and stigmasta-4-en-3-one. Of these, only the aqueous extract was active. It inhibited the binding of 125I-SHBG to its receptor. The inhibition was dose related, starting at about 0.6 mg/ml and completely inhibited binding at 10 mg/ml.
Effects of stinging nettle root extracts and their steroidal components on the Na+,K(+)-ATPase of the benign prostatic hyperplasia.
Hirano T, Homma M, Oka K Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan. Planta Med 1994 Feb;60(1):30-3
The effects of organic-solvent extracts of Urtica dioica (Urticaceae) on the Na+,K(+)-ATPase of the tissue of benign prostatic hyperplasia (BPH) were investigated. The membrane Na+,K(+)-ATPase fraction was prepared from a patient with BPH by a differential centrifugation of the tissue homogenate. The enzyme activity was inhibited by 10(-4)-10(-5) M of ouabain. The hexane extract, the ether extract, the ethyl acetate extract, and the butanol extract of the roots caused 27.6-81.5% inhibition of the enzyme activity at 0.1 mg/ml. In addition, a column extraction of stinging nettle roots using benzene as an eluent afforded efficient enzyme inhibiting activity. Steroidal components in stinging nettle roots, such as stigmast-4-en-3-one, stigmasterol, and campesterol inhibited the enzyme activity by 23.0-67.0% at concentrations ranging from 10(-3)-10(-6) M. These results suggest that some hydrophobic constituents such as steroids in the stinging nettle roots inhibited the membrane Na+,K(+)-ATPase activity of the prostate, which may subsequently suppress prostate-cell metabolism and growth.
The inhibiting effects of Urtica dioica root extracts on experimentally induced prostatic hyperplasia in the mouse.
Lichius JJ, Muth C Institut fur Pharmazeutische Biologie, Philipps-Universitat, Marburg, Germany. Planta Med 1997 Aug;63(4):307-10
Extracts of stinging nettle roots (Urtica dioica L. Urticaceae) are used in the treatment of benign prostatic hyperplasia (BPH). We established a BPH-model by directly implanting an urogenital sinus (UGS) into the ventral prostate gland of an adult mouse. Five differently prepared stinging nettle root extracts were tested in this model. The 20% methanolic extract was the most effective with a 51.4% inhibition of induced growth.
Saw Palmetto, African prune and stinging nettle for Benign Prostatic Hyperplasia ( BPH)
Awang D.V.C. Canadian Pharmaceutical Journal (Canada), 1997, 130/9 (37-44+62)
Urtica dioica L.
Bombardelli E.; Morazzoni P. E. Bombardelli, Indena S.p.A., Scientific Department, Viale Ortles 12, 20139 Milan Italy Fitoterapia (Italy) 1997, 68/5 (387-402)
U. dioica L. was used as medicinal plant since ancient times. Hydroalcoholic extract of the nettle root (Urticae radix) are currently used in the therapy of micturition disorders associated with slight and moderate BPH.
Aromatase inhibitors from Urtica dioica roots
Gansser D.; Spiteller G. Lehrstuhl Organische Chemie 1, Universitat Bayreuth, NW I, Universitatsstrasse 30,D-95440 Bayreuth Germany Planta Medica (Germany) 1995, 61/2 (138-140)
Methanolic extracts of stinging nettle (Urtica dioica L.) roots were investigated for aromatase inhibition. Enzyme inhibition was detected only after appropriate chromatographic separation. Inhibitory effects on aromatase could be demonstrated in vitro for a variety of compounds belonging to different classes. The following compounds developed weak to moderate activity: secoisolariciresinol (1), oleanolic and ursolic acid (2 and 3), (9Z,11E)-13-hydroxy-9,11-octadecadienoic acid (4), and 14-octacosanol (5). Inhibitory effects on aromatase have been known to date neither for pentacyclic triterpenes nor for secondary fatty alcohols. The potential physiological significance of the above findings is discussed. Compound 5 is a previously unknown constituent of plants.
Effects of stinging nettle root extracts and their steroidal components on the Nasup +,Ksup +-ATPase of the benign prostatic hyperplasia
Hirano T.; Homma M.; Oka K. Dept. of Clinical Pharmacology, Tokyo College of Pharmacy, 1432-1 Horinouchi,Hachioji, Tokyo 192-03 Japan Planta Medica (Germany) 1994, 60/1 (30-33)
The effects of organic-solvent extracts of Urtica dioica (Urticaceae) on the Nasup +,Ksup +-ATPase of the tissue of benign prostatic hyperplasia (BPH) were investigated. The membrane Nasup +,Ksup +-ATPase fraction was prepared from a patient with BPH by a differential centrifugation of the tissue homogenate. The enzyme activity was inhibited by 10sup -sup 4-10sup -sup 5 M of ouabain. The hexane extract, the ether extract, the ethyl acetate extract, and the butanol extract of the roots caused 27.6-81.5% inhibition of the enzyme activity at 0.1 mg/ml. In addition, a column extraction of stinging nettle roots using benzene as an eluent afforded efficient enzyme inhibiting activiry. Steroidal components in stinging nettle roots, such as stigmast-4-en-3-one, stigmasterol, and campesterol inhibited the enzyme activity by 23.0-67.0% at concentrations ranging from 10sup -sup 3-10sup -sup 6 M. These results suggest that some hydrophobic constituents such as steroids in the stinging nettle roots inhibited the membrane Nasup +,Ksup +-ATPase activity of the prostate, which may subsequently suppress prostate-cell metabolism and growth.
Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).
Schottner M, Gansser D, Spiteller G Lehrstuhl Organische Chemie I, Universitat Bayreuth, Germany. Planta Med 1997 Dec;63(6):529-32
Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).
Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.
Gansser D, Spiteller G Lehrstuhl Organische Chemie I, Universitat Bayreuth, Bundesrepublik, Deutschland. Z Naturforsch [C] 1995 Jan-Feb;50(1-2):98-104
A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.
Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia ( BPH): a multicentre trial in central Europe.
Breza J; Dzurny O; Borowka A; Hanus T; Petrik R; Blane G; Chadha-Boreham H Department of Urology, University Hospital, Bratislava, Slovak Republic. Curr Med Res Opin (England) 1998, 14 (3) p127-39
Pygeum africanum extract is available as Tadenan in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS > or = 12, quality of life (QoL) score > or = 3, and maximum urinary flow < or = 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still compliant, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.
Phytotherapy of benign prostatic hyperplasia (BPH) with Cucurbita, Hypoxis, Pygeum, Urtica and Sabal serrulata (Serenoa repens)
Odenthal K.P. K.P. Odenthal, Dept. Exp. Biology, Pharmacology, MADAUS AG, Ostmerheimerstr. 198, D-51109 Cologne Germany Phytotherapy Research (United Kingdom), 1996, 10/SUPPL. 1 (S141-S143)
The enlargement of prostate (BPH) is accompanied by urge, reduced urinary flow and increased residual urine volume. The etiology is not yet clear, though many results speak for hormonal imbalance. Several herbal drugs have been applied traditionally in the therapy of BPH, i.e., preparations of Cucurbita, Hypoxis, Pygeum, Urtica and from Sabal serrulata. Among the discussed mechanisms, phytosterols are considered as active and have been found in experimental as well as in clinical investigations to interfere with either reduction of testosterone to dihydrotestosterone, sexual hormone binding globulin, aromatization of testosterone or growth factors like EGF. Additional effects have been documented in experiments speaking for immunomodulation and anti-inflammatory qualities. We demonstrate that smooth muscle contraction of rat deferential duct, guinea-pig ileum and bladder is reduced by lipophilic extract of Sabal. Both noradrenaline-induced contractions of rat deferential duct as well as contractions elicited by electrical stimulation could be reduced concentration-dependently following addition of less than or equal to 0.33 mg/ml of lipophilic Sabal serrulata extract into the bath medium. Cumulative dosing of less than or equal to 0.15 mg/ml of Sabal extract antagonized in guinea-pig ileum and bladder smooth muscular tissue contracted in KCl salt solution. Sabal extract, in concentrations identical to those published for the so-called anti-androgenic and anti-inflammatory effects, is therefore characterized by alpha-adrenoceptor antagonistic as well as calcium blocking activities. Furthermore, these findings could explain the clinically demonstrated symptomatic relief or so called release of dynamic component of BPH.
Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts.
Yablonsky F, Nicolas V, Riffaud JP, Bellamy F Laboratoires Debat, groupe Fournier, Garches, France. J Urol 1997 Jun;157(6):2381-7 Published erratum appears in J Urol 1997 Sep;158(3 Pt 1):889
The effect of a Pygeum africanum extract (Tadenan) (Pa), used in the treatment of micturition disorders associated with BPH, has been examined on the proliferation of rat prostatic stromal cells stimulated by different growth factors. EGF, bFGF, and IGF-I but not KGF are mitogenic for prostatic fibroblasts in culture. Pygeum africanum inhibits both basal and stimulated growth with IC50 values of 4.5, 7.7 and 12.6 micrograms./ml. for EGF, IGF-I and bFGF, respectively, compared to 14.4 micrograms./ml. for untreated cells, the inhibition being stronger towards EGF. Pygeum africanum inhibited the proliferation induced by TPA or PDBu in a concentration-dependent manner with IC50 values of 12.4 and 8.1 micrograms./ml. respectively. The antiproliferative effects of Pa were not ascribed to cytotoxicity. These results show that Pygeum africanum is a potent inhibitor of rat prostatic fibroblast proliferation in response to direct activators of protein kinase C, the defined growth factors bFGF, EGF and IGF-I, and the complex mixture of mitogens in serum depending on the concentration used. PKC activation appears to be an important growth factor-mediated signal transduction for this agent. These data suggest that therapeutic effect of Pygeum africanum may be due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man.
An urodynamic study of patients with benign prostatic hypertrophy treated conservatively with phytotherapy or testosterone
Flamm J.; Kiesswetter H.; Englisch M. Urol. Abt., Wilhelminenspit., Wien Austria Wien. Klin. Wochenschr. (Austria), 1979, 91/18 (622-627)
Conservative therapy of benign prostatic hypertrophy comprises the administration of oestrogens, gestagens, androgens and anti-androgens. Phytodrugs, which contain an extract of Sabal serrulatum or Pygeum Africana as active substance are without side effects and are, therefore, being used increasingly. 74 patients with irritable or obstructive bladder symptoms due to benign prostatic hypertrophy were treated with a phytodrug (Sabal serrulatum) or with testosterone throughout a period of three months. In group one (20 patients given phytodrugs and 10 patients given testosterone) clinical symptoms and measurements of residual urine, residual urine quotient, bladder capacity, micturition pressure and maximum urethral closure pressure were recorded at the beginning and at the end of therapy. In group two 28 patients were treated with the phytodrug in the first and third months with an intervening placebo trial lasting four weeks and 16 patients were given testosterone. Clinical symptoms and uroflow and residual urine only were charted in this group. None of the patients in either group showed an improvement in the urodynamic parameters of obstruction, but all patients felt a subjective alleviation of their symptoms.