Basic and Translational Science| Volume 81, ISSUE 6, P1380.e7-1380.e13, June 2013

Download started.


Saw Palmetto Extract Enhances Erectile Responses by Inhibition of Phosphodiesterase 5 Activity and Increase in Inducible Nitric Oxide Synthase Messenger Ribonucleic Acid Expression in Rat and Rabbit Corpus Cavernosum


      To evaluate whether saw palmetto extract (SPE) relaxes corpus cavernosum and explore the underlying mechanisms.


      Forty Sprague-Dawley rats and 30 New Zealand rabbits were randomly allocated into 3 SPE-treated groups (low-, middle-, and high-dose) and 1 saline-treated control group. SPE was administered intragastrically for 7 consecutive days. Another 23 rats treated with sildenafil were used to appraise the erectile response to electrical stimulation of nerves in the corpus cavernosum. The erectile functions of rats and rabbits were evaluated 24 hours after the last SPE administration or 15 minutes after intragastric sildenafil. Outcome measures included corpus cavernosum electrical activity recording, phosphodiesterase 5 (PDE5) activity detected by the colorimetric quantitative method, and messenger ribonucleic acid (mRNA) expression level for PDE5 and inducible nitric oxide synthase (iNOS) determined using real-time polymerase chain reaction.


      In the SPE-treated animals, the relaxant response to electrical stimulation of nerves in the corpus cavernosum, reflected by the amplitude of the electrical activity within the cavernosum, was significantly and dose-dependently augmented. Similar effects were observed in the sildenafil-treated rats. PDE5 activity in rat and rabbit corpus cavernosum tissues was significantly and dose-dependently inhibited in SPE-treated animals, whereas the iNOS mRNA level increased compared with the saline group. PDE5 mRNA, however, was only significantly enhanced in the rats treated with the middle dose of SPE.


      The results suggest that SPE may have potential application value for the prevention or treatment of erectile dysfunction through an increase in iNOS mRNA expression and inhibition of PDE5 activity in corpus cavernosum smooth muscles.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wagner G.
        • Saenz de Tejada I.
        Update on male erectile dysfunction.
        BMJ. 1998; 316: 678-682
        • La Vignera S.
        • Condorelli R.
        • Vicari E.
        • et al.
        Physical activity and erectile dysfunction in middle-aged men.
        J Androl. 2012; 33: 154-161
        • Feldman H.A.
        • Goldstein I.
        • Hatzichristou D.G.
        • et al.
        Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.
        J Urol. 1994; 151: 54-61
        • Fusco F.
        • Razzoli E.
        • Imbimbo C.
        • et al.
        A new era in the treatment of erectile dysfunction: chronic phosphodiesterase type 5 inhibition.
        BJU Int. 2010; 105: 1634-1639
        • Lasker G.F.
        • Maley J.H.
        • Kadowitz P.J.
        A review of the pathophysiology and novel treatments for erectile dysfunction.
        Adv Pharmacol Sci. 2010; 2010: 1-10
        • Wilt T.J.
        • Ishani A.
        • Stark G.
        • et al.
        Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review.
        JAMA. 1998; 280: 1604-1609
        • Gacci M.
        • Corona G.
        • Salvi M.
        • et al.
        A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia.
        Eur Urol. 2012; 61: 994-1003
        • McNicholas T.
        • Kirby R.
        Benign prostatic hyperplasia and male lower urinary tract symptoms (LUTS).
        Clin Evid. 2011; 8: 1801-1840
        • Plosker G.L.
        • Brogden R.N.
        Serenoa repens (permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia.
        Drugs Aging. 1996; 9: 379-395
        • Boyle P.
        • Robertson C.
        • Lowe F.
        • et al.
        Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia.
        BJU Int. 2004; 93: 751-756
        • Geavlete P.
        • Multescu R.
        • Geavlete B.
        Serenoa repens extract in the treatment of benign prostatic hyperplasia.
        Ther Adv Urol. 2011; 3: 193-198
        • Zlotta A.R.
        • Teillac P.
        • Raynaud J.P.
        • et al.
        Evaluation of male sexual function in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), tamsulosin or finasteride.
        Eur Urol. 2005; 48: 269-276
        • Scheepe J.R.
        • Junemann K.P.
        • Buhrle C.P.
        • et al.
        Recording the corpus cavernosum electromyogram: principles and problems.
        J Urol. 1996; 155: 2074-2079
        • Quinlan D.M.
        • Nelson R.J.
        • Partin A.W.
        • et al.
        The rat as a model for the study of penile erection.
        J Urol. 1989; 141: 656-661
        • Steers W.D.
        Viagra-after one year.
        Urology. 1999; 54: 12-17
        • Gemalmaz H.
        • Waldeck K.
        • Chapman T.N.
        • et al.
        In vivo and in vitro investigation of the effects of sildenafil on rat cavernous smooth muscle.
        J Urol. 2001; 165: 1010-1014
        • Lue T.F.
        Neurogenic erectile dysfunction.
        Clin Auton Res. 2001; 11: 285-294
        • Awad A.
        • Alsaid B.
        • Bessede T.
        • et al.
        Evolution in the concept of erection anatomy.
        Surg Radiol Anat. 2011; 33: 301-312
        • Gocmez S.S.
        • Utkan T.
        • Gacar N.
        • et al.
        Chronic administration of fluoxetine impairs neurogenic and endothelium-dependent relaxation of the rabbit corpus cavernosum smooth muscle.
        Eur J Pharmacol. 2011; 670: 224-228
        • Pickard R.S.
        • Powell P.H.
        • Zar M.A.
        Nitric oxide and cyclic GMP formation following relaxant nerve stimulation in isolated human corpus cavernosum.
        Br J Urol. 1995; 75: 516-522
        • Gur S.
        • Kadowitz P.J.
        • Gurkan L.
        • et al.
        Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil.
        BJU Int. 2010; 106: 78-83
        • Phe V.
        • Roupret M.
        Erectile dysfunction and diabetes: a review of the current evidence-based medicine and a synthesis of the main available therapies.
        Diabetes Metab. 2012; 38: 1-13
        • Gonzalez-Cadavid N.F.
        • Rajfer J.
        The pleiotropic effects of inducible nitric oxide synthase (iNOS) on the physiology and pathology of penile erection.
        Curr Pharm Des. 2005; 11: 4041-4046
        • Garban H.
        • Marquez D.
        • Magee T.
        • et al.
        Cloning of rat and human inducible penile nitric oxide synthase. Application for gene therapy of erectile dysfunction.
        Biol Reprod. 1997; 56: 954-963
        • Chancellor M.B.
        • Tirney S.
        • Mattes C.E.
        • et al.
        Nitric oxide synthase gene transfer for erectile dysfunction in a rat model.
        BJU Int. 2003; 91: 691-696
        • Ferrini M.G.
        • Rivera S.
        • Moon J.
        • et al.
        The genetic inactivation of inducible nitric oxide synthase (iNOS) intensifies fibrosis and oxidative stress in the penile corpora cavernosa in type 1 diabetes.
        J Sex Med. 2010; 7: 3033-3044
        • Keravis T.
        • Lugnier C.
        Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments.
        Br J Pharmacol. 2012; 165: 1288-1305
        • Lau L.C.
        • Adaikan P.G.
        Mechanisms of direct relaxant effect of sildenafil, tadalafil and vardenafil on corpus cavernosum.
        Eur J Pharmacol. 2006; 541: 184-190
        • El-Thaher T.S.
        • Khatib S.
        • Saleem M.
        • et al.
        A novel compound JPM8: in vivo penile activity promotion in rats, effect on the relaxation and cGMP/cAMP accumulation in isolated rabbit corpora cavernosa.
        Int J Impot Res. 2002; 14: 453-461
        • Toque H.A.
        • Priviero F.B.
        • Zemse S.M.
        • et al.
        Effect of the phosphodiesterase 5 inhibitors sildenafil, tadalafil and vardenafil on rat anococcygeus muscle: functional and biochemical aspects.
        Clin Exp Pharmacol Physiol. 2009; 36: 358-366