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Choi, Kim, and Park: Quercetin Relaxed the Smooth Muscle of Rabbit Penile Corpus Cavernosum by Activating the NO-cGMP Signaling Pathway
Original Article

Natural Product Sciences 2017;23(3):169-174.

Published online: 20 January 2017

DOI: https://doi.org/10.20307/nps.2017.23.3.169

Quercetin Relaxed the Smooth Muscle of Rabbit Penile Corpus Cavernosum by Activating the NO-cGMP Signaling Pathway

Bo Ram Choi1, Hye Kyung Kim2, ∗, Jong Kwan Park1, ∗

1Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, 20, Geonji-ro, Deokjin-gu, Jeonju 54896, Korea

2College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Nam-gu, Busan 48434, Korea

∗Author for correspondence Jong Kwan Park, Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 54896, Korea. Tel: +82-63-250-1510; E-mail: rain@chonbuk.ac.kr

Received 10 April 2017       Revised 8 May 2017       Accepted 8 May 2017

Copyright © 2017 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin (10−7, 10−6, 10−5 and 10−4 M). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.

Keywords: Quercetin, Penile corpus cavernosum smooth muscle, NO-cGMP pathway, Phosphodiesterase type 5 inhibitors

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Fig. 1.
The structure of quercetin.
nps-23-169f1.tif
Fig. 2.
Relaxation effect of quercetin in L-phenylephrine (Phe)-induced contraction (n = 4). PCCSM contracted by Phe (10−5 M) that was preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10−3 M) (a) or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10−5 M) (b) was treated with four concentrations of quercetin (10−7, 10−6, 10−5 and 10−4 M). The submaximal penile contractile responses induced by Phe were taken as the 100% values, and all subsequent responses to quercetin were expressed as a percentage of this value. Each point represents the mean ± SD of the percentages. Statistical analysis was carried out by ANOVA, followed by Bonferroni's test (∗p < 0.05 compared to quercetin, ∗∗p < 0.01 compared to quercetin).
nps-23-169f2.tif
Fig. 3.
Effect of quercetin (10−7, 10−6, 10−5 and 10−4 M) on the cGMP level in the perfusate. Each point represents the mean ± SD of the percentages. Statistical analysis was carried out by ANOVA, followed by Bonferroni's test (∗p < 0.05 compared to control, ∗∗p < 0.01 compared to control).
nps-23-169f3.tif
Fig. 4.
Interaction of quercetin (QUER, 10−5 M) with sildenafil (SILD, 10−8 M) (n=4). SILD+QUER indicates quercetin-induced relaxation in sildenafil citrate-preincubated PCCSM. QUER + SILD indicates sildenafil citrate-induced relaxation in QUER-preincubated PCCSM. Each point represents the mean ± SD of percentages of maximal relaxation of the preceding submaximal contractile responses. Statistical analysis was carried out by ANOVA, followed by Bonferroni's test (∗∗p < 0.01 compared to SILD).
nps-23-169f4.tif
Fig. 5.
Interaction of quercetin (QUER, 10−5 M) with udenafil (UDE, 10−7 M) (n=4). UDE+QUER indicates quercetin-induced relaxation in udenafil-preincubated PCCSM. QUER+UDE indicates udenafil-induced relaxation in QUER-preincubated PCCSM. Each point represents the mean ± SD of percentages of maximal relaxation of the preceding submaximal contractile responses. Statistical analysis was carried out by ANOVA, followed by Bonferroni's test (∗∗p < 0.01 compared to UDE).
nps-23-169f5.tif
Fig. 6.
Interaction of quercetin (QUER, 10−5 M) with mirodenafil (MIRO, 10−8 M) (n=4). MIRO+QUER indicates quercetin-induced relaxation in mirodenafil hydrochloride-preincubated PCCSM. QUER+MIRO indicates mirodenafil hydrochloride-induced relaxation in QUER-preincubated PCCSM. Each point represents the mean ± SD of percentages of maximal relaxation of the preceding submaximal contractile responses. Statistical analysis was carried out by ANOVA, followed by Bonferroni's test (∗∗p < 0.01 compared to MIRO).
nps-23-169f6.tif
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