Aim: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. Materials and Methods: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10–6–10–2M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (Pves) and urethral perfusion pressure (UPP). Results: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10–3M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10–2M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline Pves than the PBOO group. Conclusions: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.

Keywords:
Benign prostatic hyperplasia, Ginseng, Saponin, Nitric oxide, Lower urinary tract symptoms
1.
Fathian-Sabet B, Bloch W, Klotz T, Niggemann S, Jacobs G, Addicks K, Engelmann U: Localization of constitutive nitric oxide synthase isoforms and the nitric oxide target enzyme soluble guanylyl cyclase in the human bladder. J Urol 2001;165:1724–1729.
2.
Ho MH, Bhatia NN, Khorram O: Physiologic role of nitric oxide and nitric oxide synthase in female lower urinary tract. Curr Opin Obstet Gynecol 2004;16:423–429.
3.
Tamaoki J, Nakata J, Kawatani K, Tagaya E, Nagai A: Ginsenoside-induced relaxation of human bronchial smooth muscle via release of nitric oxide. Br J Pharmacol 2000;130:1859–1864.
4.
Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–2012.
5.
Aikawa K, Chichester P, Whitbeck C, Levin RM: Effect of nitric oxide synthase inhibition on changes induced by estradiol in bladders from ovariectomized rabbits. Urol Int 2005;75:133–138.
6.
Helms S: Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev 2004;9:259–274.
7.
Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS, Yuan CS: Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 2002;51:1851–1858.
8.
Bae EA, Park SY, Kim DH: Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 2000;23:1481–1485.
9.
Bae EA, Han MJ, Choo MK, Park SY, Kim DH: Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002;25:58–63.
10.
Sparg SG, Light ME, van Staden J: Biological activities and distribution of plant saponins. J Ethnopharmacol 2004;94:219–243.
11.
Sahu NP, Banerjee S, Mondal NB, Mandal D: Steroidal saponins. Fortschr Chem Org Naturst 2008;89:45–141.
12.
Chen X, Lee TJ: Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br J Pharmacol 1995;115:15–18.
13.
Kim HJ, Woo DS, Lee G, Kim JJ: The relaxation effects of ginseng saponin in rabbit corporal smooth muscle: is it a nitric oxide donor? Br J Urol 1998;82:744–748.
14.
Ahn TY KS, Kim CS, Park TH, Park HS: The effect of ginseng on the relaxation of the penile corpus cavernosal smooth muscle in rabbits. Korean J Ginseng Sci 1996;20:339–343.
15.
Kang YJ, Sohn JT, Chang KC: Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation. Life Sci 2005;77:74–84.
16.
Kim SO, Kim MK, Lee HS, Park JK, Park K: The effect of Korean red ginseng extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism. J Sex Med 2008;5:2079–2084.
17.
Bae JH, Jung PB, Lee JG: The effects of alpha-adrenoceptor antagonists on the urethral perfusion pressure of the female rat. BJU Int 2005;96:1131–1135.
18.
Gillis CN: Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1–8.
19.
Andersson KE, Garcia Pascual A, Persson K, Forman A, Tottrup A: Electrically-induced, nerve-mediated relaxation of rabbit urethra involves nitric oxide. J Urol 1992;147:253–259.
20.
Bennett BC, Kruse MN, Roppolo JR, Flood HD, Fraser M, de Groat WC: Neural control of urethral outlet activity in vivo: role of nitric oxide. J Urol 1995;153:2004–2009.
21.
Garcia-Pascual A, Costa G, Labadia A, Persson K, Triguero D: Characterization of nitric oxide synthase activity in sheep urinary tract: functional implications. Br J Pharmacol 1996;118:905–914.
22.
Himi T, Saito H, Nishiyama N: Effect of ginseng saponins on the survival of cerebral cortex neurons in cell cultures. Chem Pharm Bull (Tokyo) 1989;37:481–484.
23.
Wen TC, Yoshimura H, Matsuda S, Lim JH, Sakanaka M: Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia. Acta Neuropathol 1996;91:15–22.
24.
Liu GY, Li XW, Wang NB, Zhou HY, Wei W, Gui MY, Yang B, Jin YR: Three new dammarane-type triterpene saponins from the leaves of Panax ginseng C.A. Meyer. J Asian Nat Prod Res 2010;12:865–873.
25.
Helmes E, Lewis VE, Allan A: Australian lawyers’ views on competency issues in older adults. Behav Sci Law 2004;22:823–831.
26.
Tang W, Eisenbrand G: Panax ginseng C.A. Meyer; in: Chinese Drugs of Plant Origin. London, Springer, 1992, pp 711–737.
27.
Matsuda H, Tong CN, Kubo M: Pharmacological study on Panax ginseng C. A. Meyer. XIV. Effect of 70% methanolic extract from red ginseng on the cytocidal effect of mitomycin c against rat ascites hepatoma AH 130 (in Japanese). Yakugaku Zasshi 1992;112:846–855.
28.
McVary KT: Medical therapy for benign prostatic hyperplasia progression. Curr Urol Rep 2002;3:269–275.
29.
Milani S, Djavan B: Lower urinary tract symptoms suggestive of benign prostatic hyperplasia: latest update on alpha-adrenoceptor antagonists. BJU Int 2005;95(suppl 4):29–36.
30.
Mumtaz FH, Khan MA, Thompson CS, Morgan RJ, Mikhailidis DP: Nitric oxide in the lower urinary tract: physiological and pathological implications. BJU Int 2000;85:567–578.
31.
Masuda H, Tsujii T, Okuno T, Kihara K, Goto M, Azuma H: Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity in the impaired neurogenic relaxation of the rabbit proximal urethra with ischaemia. Br J Pharmacol 2001;133:97–106.
32.
Nishizawa S, Igawa Y, Okada N, Ohhashi T: Capsaicin-induced nitric-oxide-dependent relaxation in isolated dog urethra. Eur J Pharmacol 1997;335:211–219.
33.
Gillespie JS, Liu XR, Martin W: The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol 1989;98:1080–1082.
34.
Huang A, Palmer LS, Hom D, Valderrama E, Trachtman H: The role of nitric oxide in obstructive nephropathy. J Urol 2000;163:1276–1281.
35.
Kozlowski R, Kershen RT, Siroky MB, Krane RJ, Azadzoi KM: Chronic ischemia alters prostate structure and reactivity in rabbits. J Urol 2001;165:1019–1026.
36.
Ihm DH, Chung HC, Song JM: Expression of nitric oxide synthase (NOS) in rat bladders subjected to short-term partial outlet obstruction. Korean J Urol 2008;49:622.
37.
Guan YY, Kwan CY, He H, Sun JJ, Daniel EE: Effects of Panax notoginseng saponins on receptor-operated Ca2+ channels in vascular smooth muscle. Zhongguo Yao Li Xue Bao 1994;15:392–398.
38.
Li Z, Chen X, Niwa Y, Sakamoto S, Nakaya Y: Involvement of Ca2+-activated K+ channels in ginsenosides-induced aortic relaxation in rats. J Cardiovasc Pharmacol 2001;37:41–47.
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2012
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