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Penile erection induced by scoparone from Artemisia capillaris through NO-cGMP signaling pathway

Choi, BR1; Kim, HK2; Shin, YS1; Chae, MR3; Lee, SW3; Yang, SK4; Park, KS5; Park, JK1

1: 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, Jeonju, Korea.; 2: College of Pharmacy, Kyungsung University, Busan, Korea.; 3: Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University Medical School, Samsung Medical Center, Seoul, Republic of Korea.; 4: Department of Urology, College of Medicine, Konkuk University Chungju Hospital,Chungju, Republic of Korea.; 5: Department of Urology, Chonnam National University Medical School, Gwangju, Republic of Korea.

Objective: The objective of this study was to evaluate relaxant effect of scoparone from Artemisia capillaris on rabbit penile corpus cavernosum smooth muscle (PCCSM) and elucidate the mechanism of action of scoparone for the treatment of erectile dysfunction (ED).

Material and Method: The precontracted PCCSM with phenylephrine (Phe) was treated with 3 Artemisia herbs (A. princeps, A. capillaris and A. iwayomogi) and 3 fractions (n-hexane, ethyl acetate and n-butanol fractions) with different concentrations (0.1, 0.5, 1 and 2 mg/mL). 4 components (esculetin, scopoletin, capillarisin and scoparone) isolated from A. capillaris also evaluted. PCCSM was preincubated with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cyclic nucleotide in the perfusate was measured by radioimmunoassay. The interaction between scoparone with udenafil or rolipram was also evaluated.

Result: A. capillaris extract relaxed PCCSM in a concentration-dependent manner. Scoparone had the highest relaxant effect on PCCSM among four components (esculetin, scopoletin, capillarisin and scoparone) isolated from ethyl acetate fraction. The application of scoparone on PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Scoparone also increased the cGMP of perfusate in a concentration-dependent manner. Furthermore, scoparone enhanced the udenafil or rolipram-induced relaxation on PCCSM.

Conclusion: Scoparone relaxed the PCCSM mainly by activating NO-cGMP signaling pathway and it may be a new promising treatment for ED patients who do not completely respond to udenafil.


Work supported by industry: yes, by This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C0018). The funders had no r (industry funding only - investigator initiated and executed study).

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