Nutr Res Pract.  2018 Aug;12(4):291-297. 10.4162/nrp.2018.12.4.291.

Effects of Schisandra chinensis fruit extract and gomisin A on the contractility of penile corpus cavernosum smooth muscle: a potential mechanism through the nitric oxide - cyclic guanosine monophosphate pathway

• Choi BR
• Kim HK
• Park JK

• KMID: 2420994
• DOI: http://doi.org/10.4162/nrp.2018.12.4.291

Abstract

BACKGROUND/OBJECTIVES
This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM).
MATERIALS/METHODS
PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram.
RESULTS
Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways.
CONCLUSIONS
The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.

Keyword

Nitric oxide; lignans; erectile dysfunction; PDE5 inhibitors

MeSH Terms

Adenylyl Cyclases
Biological Products
Blotting, Western
Cyclic AMP-Dependent Protein Kinases
Erectile Dysfunction
Fruit*
Guanosine Monophosphate*
Guanosine*
Guanylate Cyclase
Humans
Lignans
Male
Muscle, Smooth*
Neurons
Nitric Oxide Synthase
Nitric Oxide*
Perfusion
Phosphodiesterase 5 Inhibitors
Radioimmunoassay
Relaxation
Rolipram
Schisandra*
Adenylyl Cyclases
Biological Products
Cyclic AMP-Dependent Protein Kinases
Guanosine
Guanosine Monophosphate
Guanylate Cyclase
Lignans
Nitric Oxide
Nitric Oxide Synthase
Phosphodiesterase 5 Inhibitors
Rolipram

Figure

• 

  Fig. 1 Relaxation effect of SC in Phe-induced contraction (n = 4). PCCSM contracted by Phe (10−5 M) was pretreated with ODQ (A, 10−5 M), L-NAME (B, 10−3 M), MDL 12330A (C, 10−5 M) or H-89(D, 10−4 M), and subsequently exposed to four concentrations of SC (0.1, 0.5, 1 and 2 mg/mL). SC: Schisandra chinensis; Phe: L-phenylephrine; PCCSM: penile corpus cavernosum smooth muscle; ODQ: 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one; L-NAME: Nω-Nitro-L-arginine methyl ester hydrochloride; MDL 12330A: MDL 12330A hydrochloride; H-89: H-89 dihydrochloride hydrate. Values are mean ± SD. *,**Statistically significant from SC. *P < 0.05, **P < 0.01.

• 

  Fig. 2 Relaxation effect of GA in Phe-induced contraction (n = 4). PCCSM contracted by Phe (10−5 M) was pretreated with ODQ (A, 10−5 M), L-NAME (B, 10−3 M), MDL 12330A (C, 10−5 M) or H-89(D, 10−4 M), and subsequently exposed to four concentrations of GA (10−7, 10−6, 10−5 and 10−4 M). GA: gomisin A; Phe: L-phenylephrine; PCCSM: penile corpus cavernosum smooth muscle; ODQ: 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one; L-NAME: Nω-Nitro-L-arginine methyl ester hydrochloride; MDL 12330A: MDL 12330A hydrochloride; H-89: H-89 dihydrochloride hydrate. Values are mean ± SD. *,**Statistically significant from GA. *P < 0.05, **P < 0.01.

• 

  Fig. 3 Effects of L-NAME (10−3 M) in SC (A, 1 mg/mL) or GA (B, 10−5 M) induced eNOS and nNOS protein in the PCCSM by western blotting (n = 4). L-NAME: Nω-Nitro-L-arginine methyl ester hydrochloride; SC: Schisandra chinensis; GA: gomisin A; eNOS: endothelial nitric oxide synthase; nNOS: neuronal nitric oxide synthase; PCCSM: penile corpus cavernosum smooth muscle. Values are mean ± SD. *Statistically significant from GA, P < 0.05.

• 

  Fig. 4 Interaction of SC (1 mg/mL) with UDE (10−7 M) or Rol (10−6 M) (n = 4). SC: Schisandra chinensis; UDE: udenafil; Rol: rolipram; UDE + SC: SC induced relaxation in the UDE-pretreated PCCSM (A); SC + UDE: UDE induced relaxation in the SC-pretreated PCCSM (A); Rol + SC: SC induced relaxation in the Rol-pretreated PCCSM (B); SC + Rol: Rol induced relaxation in the SC-pretreated PCCSM (B). Values are mean ± SD. **Statistically significant from Ude or Rol, P < 0.01.

• 

  Fig. 5 Interaction of GA (10−5 M) with UDE (10−7 M) or Rol (10−6 M) (n = 4). GA: gomisin A; UDE: udenafil; Rol: rolipram; UDE + GA: GA induced relaxation in the UDE-pretreated PCCSM (A); GA + UDE: UDE induced relaxation in the GA-pretreated PCCSM (A); Rol + GA: GA induced relaxation in the Rol-pretreated PCCSM (B); GA + Rol: Rol induced relaxation in the GA-pretreated PCCSM (B). Values are mean ± SD. **Statistically significant from Ude or Rol, P < 0.01.

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