Korean J Urol.  2013 Mar;54(3):183-188.

Effects and Mechanism of Action of a Tribulus terrestris Extract on Penile Erection

• Do J
• Choi S
• Choi J
• Hyun JS

Abstract

PURPOSE
Tribulus terrestris has been used as an aphrodisiac. However, little is known about the effects and mechanism of action of T. terrestris on penile erection. Therefore, the effect of a T. terrestris extract and the mechanism of action of the extract on relaxation of the corpus cavernosum (CC) were investigated. The erectogenic effects of an oral preparation of the extract were also assessed.
MATERIALS AND METHODS
The relaxation effects and mechanism of action of the T. terrestris extract on rabbit CC were investigated in an organ bath. The intracavernous pressure (ICP) was calculated after oral administration of the extract for 1 month to evaluate whether the relaxation response of the CC shown in the organ bath occurred in vivo. Additionally, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in the CC by immunoassay. Smooth muscle relaxation was expressed as the percentage decrease in precontraction induced by phenylephrine. The ICP was also assessed in rats after oral administration of the extract for 1 month, and changes in concentrations of cGMP and cAMP were monitored.
RESULTS
Concentration-dependent relaxation effects of the extract on the CC were detected in the organ bath study. Relaxation of the CC by the T. terrestris extract was inhibited in both an endothelium-removed group and an L-arginen methyl ester pretreatment group. The ICP measured after oral administration of the T. terrestris extract for 1 month was higher than that measured in the control group, and a significant increase in cAMP was observed in the T. terrestris extract group.
CONCLUSIONS
The T. terrestris extract induced concentration-dependent relaxation of the CC in an organ bath. The mechanism included a reaction involving the nitric oxide/nitric oxide synthase pathway and endothelium of the CC. Moreover, in an in vivo study, the T. terrestris extract showed a significant concentration-dependent increase in ICP. Accordingly, the T. terrestris extract may improve erectile function.

Keyword

Penile erection; Smooth muscle; Tribulus

MeSH Terms

Adenosine Monophosphate
Administration, Oral
Animals
Endothelium
Guanosine Monophosphate
Immunoassay
Male
Muscle, Smooth
Penile Erection
Phenylephrine
Rats
Relaxation
Tribulus
Adenosine Monophosphate
Guanosine Monophosphate
Phenylephrine

Figure

• 

  FIG. 1 Relaxation effects of the Tribulus terrestris extract (mg/mL) on phenylephrine (PE) contraction (5×10-6 M) in rabbit corpus cavernosum. The T. terrestris extract showed a concentration-dependent relaxation response beginning at 0.25 mg/mL (p<0.05).

• 

  FIG. 2 Effects of a Tribulus terrestris extract on the relaxation response of the rat corpus cavernosum (CC). The relaxation response of the CC was suppressed only by the nitric oxide synthesis inhibitor L-arginine methyl ester (L-NAME) and endothelium-denuded [E (-)] CC. Pretreatment with indomethacin (Indome), glibenclamide (GB), 4-aminopyridine (4-AP), or methylene blue (MB) for 30 minutes did not suppress the relaxation of the CC by the T. terrestris extract (p<0.05, n=8/group). PE, phenylephrine. *,†p<0.05.

• 

  FIG. 3 Changes in intracavernous pressure (ICP) after oral administration of the Tribulus terrestris extract for 1 month. The graph shows an increase in ICP in response to carvernosal nerve stimulation in all groups. The maximum ICP/mean systemic arterial blood pressure (MAP) showed a significant concentration-dependent increase beginning at 2.5 mg/kg compared with that in the control group (p<0.05, n=8/group). *p<0.05.

• 

  FIG. 4 Changes in the cyclic adenosine monophosphate (cAMP) (A) and cyclic guanosine monophosphate (cGMP) (B) concentrations in the corpus cavernosum (CC) of rats (n=8/group) after oral administration of the Tribulus terrestris extract for 1 month. The cAMP concentration showed a statistically significant increase compared with that in the control group, but the difference was not significant for cGMP. *p<0.05.

Reference

1. Gholamine B, Shafiei M, Motevallian M, Mahmoudian M. Effects of pioglitazone on erectile dysfunction in sildenafil poor-responders: a randomized, controlled study. J Pharm Pharm Sci. 2008. 11:22–31.

2. Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction: an evaluation using primates, rabbit and rat. Phytomedicine. 2008. 15:44–54.

3. Gauthaman K, Adaikan PG, Prasad RN. Aphrodisiac properties of Tribulus terrestris extract (Protodioscin) in normal and castrated rats. Life Sci. 2002. 71:1385–1396.

4. Martino-Andrade AJ, Morais RN, Spercoski KM, Rossi SC, Vechi MF, Golin M, et al. Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats. J Ethnopharmacol. 2010. 127:165–170.

5. Bagcivan I, Gokce G, Yildirim S, Sarioglu Y. Investigation of the mechanism of nicotine induced relaxation in rabbit corpus cavernosum in vitro. Urol Res. 2004. 32:209–212.

6. Utkan NZ, Utkan T, Sarioglu Y, Canturk NZ, Okay E. Investigation of the mechanism of nicotine-induced relaxation in guinea pig gallbladder. J Surg Res. 2003. 110:272–275.

7. Skiker M, Mekhfi H, Aziz M, Haloui B, Lahlou S, Legssyer A, et al. Artemisia herba-alba Asso relaxes the rat aorta through activation of NO/cGMP pathway and K(ATP) channels. J Smooth Muscle Res. 2010. 46:165–174.

8. Diederichs W, Stief CG, Lue TF, Tanagho EA. Norepinephrine involvement in penile detumescence. J Urol. 1990. 143:1264–1266.

9. Gauthaman K, Ganesan AP, Prasad RN. Sexual effects of puncturevine (Tribulus terrestris) extract (protodioscin): an evaluation using a rat model. J Altern Complement Med. 2003. 9:257–265.

10. Arsyad KM. Effect of protodioscin on the quantity and quality of sperms from males with moderate idiopathic oligozoospermia. Medika. 1996. 22:614–618.

11. El-Tantawy WH, Temraz A, El-Gindi OD. Free serum testosterone level in male rats treated with Tribulus alatus extracts. Int Braz J Urol. 2007. 33:554–558.

12. Burnett AL. Nitric oxide in the penis: physiology and pathology. J Urol. 1997. 157:320–324.

13. Hedlund P, Aszodi A, Pfeifer A, Alm P, Hofmann F, Ahmad M, et al. Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proc Natl Acad Sci U S A. 2000. 97:2349–2354.