-IBIS-1.7.0-
rx
herb
Serenoa spp. (Saw Palmetto)
Botanicals

definition

botanical name(s): Serenoa serrulata, Serenoa repens, Sagal serrulata
synonyms: saw palmetto
part(s) used: berries gathered in the fall
qualities: pungent, sweet, warm
affinities: urogenital system
actions: diuretic, nerve sedative, expectorant, nutritive tonic (Felter and Scudder), urinary antiseptic, gastrointestinal stimulant (Anderson Geller), tissue builder, endocrine agent (Hoffman), circulatory stimulant. Reported aphrodisiac. Tonic to nasal and urogenitary mucous membranes. Reported anabolic agent.
dosage:
» decoction: half to 1 tsp. to one cup water; drink 1 cup three times daily.
» powder: 0.5 - 1 g.
» tincture: 1 - 3 ml. three times daily
» standardised extract:
specific indications:
Benign prostatic hypertrophy (BPH)
therapy: prostate conditions (BPH, prostatitis), enuresis, stress incontinence (Anderson Geller); catarrhal secretions with relaxation and laxity (Felter and Scudder), infections of genitourinary tract, wasting diseases, as expectorant with problems of both respiratory and genitourinary mucosa
constituents:
» Free fatty acids - C10-C18 and their methyl/ethyl esters
» Long chain alcohols - C22-C30, + polyprenols
» Phytosterols - inc b sitosterol, stigmasterol many as esters of FA’s Hence Liposterolic fraction ~85% FA’s sterols is used as standard. Plant content <1.5%
» Misc - polysacharrides, resins, fixed oils
clinical trials:
A recent (Wilt, 1998) metastudy of 18 controlled clinical studies (n=2939)concluded that saw palmetto was at least as effective as finasteride and with less side effects ( erectile dysfunction).
AHPA Botanical Safety Rating: 1
toxicity: 0


footnotes

Adriazola Semino M, Lozano Ortega JL, Garcia Cobo E, Tejeda Banez E, Romero Rodriguez F. [Symptomatic treatment of benign hypertrophy of the prostate. Comparative study of prazosin and serenoa repens]. Arch Esp Urol 1992 Apr;45(3):211-213. [Article in Spanish]
Abstract: Forty-five patients diagnosed as having BPH and clinically diagnosed micturition disorders were entered in a therapeutic protocol. Twenty-five patients received Prazosin and the remaining 20 patients were treated with Serenoa Repens for a period of 12 weeks. The symptomatology was assessed by flowmetry and the patients were questioned as to the irritative symptoms. It can be concluded from the study that Prazosin is slightly more effective in controlling the irritative symptoms produced by BPH.

Anderson Geller, C. 1984-1989. Lectures in Botanical Medicine, National College of Naturopathic Medicine. Portland, OR.

Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Lancet 1995 Jun 17;345(8964):1529-1532.
Abstract: Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.

Braeckman J. The extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a multicenter open study. Curr Ther Res 1994;55:776-785.

Breu W, Hagenlocher M, Redl K, Tittel G, Stadler F, Wagner H. [Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism]. [Article in German] Arzneimittelforschung 1992 Apr;42(4):547-551.
Abstract: The extract SG 291 (Talso, Talso uno) from the fruits of Sabal serrulata (syn.: Serenoa repens) prepared by supercritical fluid extraction with carbon dioxide is used for the treatment of benign prostatic hyperplasia (BPH) and non bacterial prostatitis. In the present work, the Sabal extract SG 291 was analyzed by gas chromatography and investigated for its inhibitory influence on the biosynthesis of inflammatory arachidonic acid metabolites. The extract SG 291 was found in vitro to be a dual inhibitor of the cyclooxygenase (IC50-value: 28.1 micrograms/ml) and 5-lipoxygenase pathway (IC50-value: 18.0 micrograms/ml). By alkaline hydrolysis, ether extraction and preparative thin layer chromatography the extract SG 291 was separated in three fractions containing acid lipophilic compounds (A), fatty alcohols (B) and sterols (C) as main components. Fraction A inhibited the biosynthesis of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) metabolites in the same intensity as the native extract SG 291, while the fractions B, C and beta-sitosterol showed no inhibitory effect on both enzymes of the arachidonic acid pathways. Therefore, the CO and 5-LO inhibiting principle of Sabal serrulata extract SG 291 must be localized in the acidic lipophilic fraction (SLF). The CO and 5-LO inhibitory effects may give an explanation for the in vivo observed antiphlogistic and antiedematous activity of the lipophilic Sabal serrulata extract SG 291.

Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostatic hyperplasia: a randomized international study of 1,098 patients. Eur Urol 1996;30:52:76 (abstract 240).

Casarosa C, Cosci di Coscio M, Fratta M. Lack of effects of a lyposterolic extract of Serenoa repens on plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone. Clin Ther 1988;10(5):585-588.
Abstract: Twenty men, aged 50 to 75 years (mean, 67 years), suffering from benign prostatic hypertrophy received 160 mg of a lyposterolic extract of Serenoa repens, twice daily for 30 days. Before and at the end of treatment, plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone were determined. No changes in plasma hormone levels occurred as a result of treatment. It is concluded that Serenoa extract, which is useful in the treatment of benign prostatic hypertrophy, does not act via systemic changes of hormone levels.

Champault G, Patel JC, Bonnard AM. A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia. Br J Clin Pharmacol 1984 Sep;18(3):461-462.

Chevalier G, Benard P, Cousse H, Bengone T. Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of Serenoa repens (Permixon) supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol. Eur J Drug Metab Pharmacokinet 1997 Jan-Mar;22(1):73-83.
Abstract: The study carried out on rats given orally the n-hexane lipido/sterolic extract of Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids or beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues shows the highest level in the case of administration of LSESR supplemented with [14C]-labelled oleic acid. This was clearly demonstrated on a rat with an induced fibro-muscular hyperplasia of the prostate and by quantitative measurements of radioactivity. Ratios of radioactivity in tissues compared to plasma show an uptake of radioactivity greater in prostate as compared to other genital organs, i.e. the seminal vesicles or to other organs such as liver.

Debrovner D. Prostate: new drugs, new tests, new hope. American Druggist. 1992;206(4):55-61.

Delos S, Carsol JL, Ghazarossian E, Raynaud JP, Martin PM. Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts. J Steroid Biochem Mol Biol 1995 Dec;55(3-4):375-83.
Abstract: We compare testosterone (T) metabolism in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH) and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts, respectively. Northern blot analysis of total RNA from epithelial cells (BPH or adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1 isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts, only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) and finasteride, inhibited DHT formation with a preferential action of 4-MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon) inhibited the formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and fibroblasts, respectively]. These results have important therapeutic implications when selecting appropriate treatment options for BPH.

Di Silverio F, D'Eramo G, Flammia GP, Buscarini M, Frascaro E, Mariani M, Sciarra A. [Pharmacological combinations in the treatment of benign prostatic hypertrophy]. J Urol (Paris) 1993;99(6):316-320. [Article in French]
Abstract: In the development of the obstructive symptomatology of benign prostatic hypertrophy (BPH), two components may be identified, mechanical and dynamic. In the mechanical component, the interaction of a stromal and a epithelial compartment determines prostatic mass growth. The dynamic component involves smooth muscle tone in the prostate and urethra. The consideration that prostatic disease is not only epithelial in origin, but also stromal, leads to the association of an antiandrogen (which acts on the epithelial component) and an antiestrogen (active on the stromal component) in the medical therapy of BPH. In 1985 we carried out a randomized study on 256 BPH patients treated with Cyproterone acetate (CPA) plus Tamoxifen (TAM). Recently, we performed a multicenter double blind study on BPH patients treated with the association CPA plus Serenoa Repens. A statistically significant difference in prostate volume reduction between the groups treated with the combinations and those with the monotherapies was observed. The development of new compounds, such as 5 alpha reductase and aromatase inhibitors, consents to introduce a combination therapy with less side effects. A second pharmacological association may be obtained with drugs acting on the mechanical and others acting on the dynamic (alpha blockers) component of BPH. This combination may associate the early symptomatic effect of alpha blockers with the long term results of a 5 alpha reductase inhibitor, antiestrogen or aromatase inhibitor.

Di Silverio F, D'Eramo G, Lubrano C, Flammia GP, Sciarra A, Palma E, Caponera M, Sciarra F. Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. Eur Urol 1992;21(4):309-314.
Abstract: A double-blind placebo-controlled study was performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving Serenoa repens extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction using the saturation analysis technique (Scatchard analysis or single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR). Scatchard analysis of ERc and Ern revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. In the untreated BPH group, ER were higher in the n than in the c fraction: Ern were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group.

Di Silverio F, Monti S, Sciarra A, Varasano PA, Martini C, Lanzara S, D'Eramo G, Di Nicola S, Toscano V. Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Prostate 1998 Oct 1;37(2):77-83.
Abstract: BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr, Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5alpha-reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed. METHODS: BPH samples were sectioned in periurethral, subcapsular, and intermediate regions: in each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges. RESULTS: In the untreated group, T, DHT, and EGF presented the highest concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue, and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated group, a statistically significant reduction was observed, mainly in the periurethral region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P < 0.001). CONCLUSIONS: The decrease of DHT and the rise of T in BPH tissue of patients treated with Permixon confirms the capacity of this drug to inhibit in vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained with finasteride, are particularly evident in the periurethral region, whose enlargement is responsible for urinary obstruction, with respect to the subcapsular region. A possible speculation is that the preferential reduction of DHT and EGF content in the periurethral region is involved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy.

Felter, H.W. and Scudder, John K., 1922. The Eclectic Materia Medica, Pharmacology and Therapeutics. Cincinnati, Ohio. Reprinted 1985, Eclectic Medical Publications, Portland, OR.

Gerber GS, Zagaja GP, Bales GT, Chodak GW, Contreras BA. Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms. Urology 1998 Jun;51(6):1003-1007.
Abstract: OBJECTIVES: To assess the effects of saw palmetto on voiding symptoms and urodynamic parameters in men with lower urinary tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH). METHODS: Fifty men with previously untreated LUTS and a minimum International Prostate Symptom Score (IPSS) of 10 or greater were treated with a commercially available form of saw palmetto (160 mg twice per day) for 6 months. The initial evaluation included measurement of peak urinary flow rate, postvoid residual urine volume, pressure-flow study, and serum prostate-specific antigen (PSA) level. Patients completed an IPSS, serum PSA was determined, and flow rate was measured every 2 months during the course of the study. A urodynamic evaluation was repeated at the completion of the 6-month trial. RESULTS: The mean IPSS (+/-SD) improved from 19.5+/-5.5 to 12.5+/-7.0 (P <0.001) among the 46 men who completed the study. Significant improvement in the symptom score was noted after treatment with saw palmetto for 2 months. An improvement in symptom score of 50% or greater after treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30% (14 of 47), and 46% (21 of 46) of patients, respectively. There was no significant change in peak urinary flow rate, postvoid residual urine volume, or detrusor pressure at peak flow among patients completing the study. No significant change in mean serum PSA level was noted. CONCLUSIONS: Saw palmetto is a well-tolerated agent that may significantly improve lower urinary tract symptoms in men with BPH. However, we were unable to demonstrate any significant improvement in objective measures of bladder outlet obstruction. Placebo-controlled trials of saw palmetto are needed to evaluate the true effectiveness of this compound.

Grasso M, Montesano A, Buonaguidi A, Castelli M, Lania C, Rigatti P, Rocco F, Cesana BM, Borghi C. Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia. Arch Esp Urol 1995 Jan-Feb;48(1):97-103.
Abstract: OBJECTIVES: Sixty-three patients suffering from benign prostatic hyperplasia (BPH) entered a double-blind, comparative, parallel-groups study lasting 3 weeks, carried out to compare the efficacy and safety of alfuzosin 2.5 mg three times daily (n = 32) vs serenoa repens 160 mg twice daily (n = 31) in BPH. METHODS: Efficacy was assessed both on clinical symptoms (Boyarsky's scale, visual analogue scale, clinical global impression), urinary flow rates (uroflowmetry) and residual urinary volume (transabdominal ultrasound). Events and reported signs were recorded throughout the entire study. RESULTS: Statistically significant and clinically relevant differences were found between the two treatments in favour of alfuzosin for Boyarsky's total score (decrease from 9.6 +/- 3.0 to 5.9 +/- 3.0, 38.8% for alfuzosin and from 9.3 +/- 2.5 to 6.8 +/- 2.8, 26.9% for serenoa repens) and obstructive score (decrease from 4.9 +/- 2.1 to 3.0 +/- 1.9, 37.8% for alfuzosin; from 4.4 +/- 1.7 to 3.4 +/- 1.8, 23.1% for Serenoa repens; p = 0.01 for both). Clinically relevant differences were found between the two treatments for visual analogue scale and overall clinical impression at the end of the study. Furthermore, the increase in quality of micturition was better with alfuzosin. The proportion of responders (increase on day 21 in peak flow rate of at least 25% relative to the baseline values) was in favour of alfuzosin (71.8% and 48.4% for alfuzosin and Serenoa repens, respectively; p = 0.057). Both treatments were well tolerated. No patient treated with alfuzosin complained of any adverse event at any time during the study. One patient in the Serenoa group complained of mild pruritus which cleared spontaneously. Systolic, diastolic blood pressure and heart rate did not show any clinically relevant change during treatment with alfuzosin. CONCLUSIONS: The findings confirm the efficacy and safety of alfuzosin in symptomatic BPH and indicate the superiority of alfuzosin over Serenoa repens in the treatment of urinary signs and symptoms of BPH.

Green L, Wysowski DK, Fourcroy JL. Gynecomastia and breast cancer during finasteride therapy. N EngI J Med 1996;335:823.

Hoffman, D. 1994. The Information Sourcebook of Herbal Medicine. The Crossing Press, Freedom, CA.

Iehle C, Delos S, Guirou O, Tate R, Raynaud JP, Martin PM. Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors. J Steroid Biochem Mol Biol 1995 Sep;54(5-6):273-279.
Abstract: The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.

Paubert-Braquet M, Cousse H, Raynaud JP, Mencia-Huerta JM, Braquet P. Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies. Eur Urol 1998;33(3):340-347.
Abstract: OBJECTIVE: To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate MATERIAL AND METHODS: Cell proliferation was assessed by incorporation of [3H]thymidine followed by historadiography. RESULTS: Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition approximately 80-95%; b-FGF, mean inhibition approximately 40-90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 micrograms/ ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 micrograms/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1-30 ng/ml), did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30 micrograms/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. CONCLUSIONS: Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.

Paubert-Braquet M, Mencia Huerta JM, Cousse H, Braquet P. Effect of the lipidic lipidosterolic extract of Serenoa repens (Permixon) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils. Prostaglandins Leukot Essent Fatty Acids 1997 Sep;57(3):299-304.
Abstract: Although the lipidic extract of Serenoa repens (LESSr, Permixon, Sereprostat) is widely used in patients suffering from benign prostatic hypertrophy (BPH), its mechanism of action is not fully elucidated. It has been demonstrated that infiltration of the prostate by inflammatory cells is one of the aetiologic factors involved in the development of BPH. These inflammatory cell types, such as polymorphonuclear neutrophils (PMNs), produce chemotactic mediators and contribute to the development of the disease. Among the chemotactic factors generated by inflammatory cell types, the derivatives of arachidonic acid have been extensively studied. For instance, leukotriene (LT) B4 is one of the most potent chemotactic factors for PMNs and also exhibits a wide range of biological activities. In order to investigate the potential action of LESSr on arachidonate metabolism, and particularly on the synthesis of LTB4, the effect of this extract on the in vitro synthesis of LT by human PMNs stimulated with the calcium ionophore A23187 was investigated. LESSr significantly inhibits the production of 5-lipoxygenase metabolites (5-HETE, 20-COOH LTB4, LTB4 and 20-OH LTB4) at concentrations as low as 5 microg/ml. Such an effect of LESSr was also observed in the presence of exogenous arachidonic acid (20 microg/ml) and when f-MLP was used as the agonist, suggesting that inhibition of LTB4 production by the extract was unrelated to phospholipase A2 blockade and independent of the stimulating agent. The capability of LESSr to antagonize 5-lipoxygenase metabolites production may contribute, at least partly, to the understanding of its therapeutic activity on the inflammatory component of BPH.

Ravenna L, Di Silverio F, Russo MA, Salvatori L, Morgante E, Morrone S, Cardillo MR, Russo A, Frati L, Gulino A, Petrangeli E. Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines. Prostate 1996 Oct;29(4):219-30.
Abstract: BACKGROUND: Permixon is a drug used in the treatment of benign prostatic hyperplasia. We studied its androgenic and antiandrogenic effects in the prostatic cell lines LNCaP and PC3, respectively responsive and unresponsive to androgen stimulation. METHODS: We performed FACScan analysis to investigate toxicity, 3H thymidine and 35S methionine incorporation to determine antiproliferative and metabolic effects, electron microscopy to study ultrastructural changes and cotransfection experiments to elucidate the role of wild type androgen receptor. RESULTS: In LNCaP cell line, Permixon induced a double proliferative/differentiative effect, not observed in PC3 cells. In PC3 cells cotransfected with wild-type androgen receptors and CAT reporter genes under the control of a androgen responsive element, the drug inhibited androgen-induced CAT transcription. CONCLUSIONS: Our data indicate a role of the androgen receptor in mediating the effects of Permixon in LNCaP cells. Cotransfection experiments in PC3 cells support a clear antiandrogenic action of the drug.

Shimada H, Tyler VE, McLaughlin JL. Biologically active acylglycerides from the berries of saw-palmetto (Serenoa repens). J Nat Prod 1997 Apr;60(4):417-418.
Abstract: Brine shrimp lethality-directed fractionation of the 95% EtOH extract of the powdered, dried berries of Serenoa repens (Bart.) Small (saw-palmetto) (Palmae) led to the isolation of two monoacylglycerides, 1-monolaurin (1) and 1-monomyristin (2). Compounds 1 and 2 showed moderate biological activities in the brine shrimp lethality test and against renal (A-498) and pancreatic (PACA-2) human tumor cells; borderline cytotoxicity was exhibited against human prostatic (PC-3) cells. The fruits and extracts of saw-palmetto are taken orally as an herbal medicine to prevent prostatic hyperplasias.

Strauch G, Perles P, Vergult G, Gabriel M, Gibelin B, Cummings S, Malbecq W, Malice MP. Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers. Eur Urol 1994;26(3):247-252.
Abstract: A total of 32 healthy male volunteers (age range 20-30 years) were enrolled in a 1-week open, randomized, placebo-controlled study comparing finasteride (Proscar), a 5 alpha-reductase inhibitor, with Permixon, the plant extract of Serenoa repens. The objective of the study was to evaluate the effect of single and multiple doses of the drugs on the inhibition of 5 alpha-reductase as assessed by serum dihydrotestosterone level determination. Following baseline measurements on day 1, the subjects were randomized to finasteride 5 mg once a day (n = 10), Permixon 80 mg x 2 twice a day (n = 11), or to placebo once a day (n = 11) for 7 days. Serum testosterone and dihydrotestosterone levels, were determined on day 1 (baseline and 12 h) and on days 2 (24 h), 3 (48 h), 4 (72 h), 6 (120 h), and 8 (168 h). After 12 h, a single dose of finasteride 5 mg reduced the serum dihydrotestosterone level by 65% (p < or = 0.01). The decreases ranged from -52 to -60% with multiple doses of finasteride 5 mg once a day (p < or = 0.01). As in the placebo group, there was no effect of Permixon on the serum dihydrotestosterone level. No significant difference was detected between finasteride and Permixon or between finasteride and placebo with respect to serum testosterone, except on days 3 and 6, respectively (p < or = 0.05). However, the corresponding serum testosterone levels remained within the normal ranges. These data confirm the efficacy of finasteride as inhibitor of 5 alpha-reductase.

Tasca A, Barulli M, Cavazzana A, Zattoni F, Artibani W, Pagano F. [Treatment of obstructive symptomatology caused by prostatic adenoma with an extract of Serenoa repens. Double-blind clinical study vs. placebo]. Minerva Urol Nefrol 1985 Jan-Mar;37(1):87-91 [Article in Italian]

Wilt TJ; Ishani A; Stark G; MacDonald R; Lau J; Mulrow C. 1998. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998 Nov 11;280(18):1604-1609.
ABSTRACT: OBJECTIVE: To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH). DATA SOURCES: Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. STUDY SELECTION: Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days. DATA EXTRACTION: Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies. DATA SYNTHESIS: A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, - 0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively. CONCLUSIONS: The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.