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Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle

International Journal of Impotence Research volume 27, pages 225–232 (2015)Cite this article

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A Corrigendum to this article was published on 11 March 2016

Abstract

The objective was to investigate the cellular effect and action mechanism of Artemisia capillaris extract (ACE) and its component, scopoletin, on penile corpus cavernosum smooth muscle (PCCSM). In vitro study with PCCSM, the precontracted PCCSM with phenylephrine was treated with ACE or scopoletin. Cyclic nucleotides in the perfusate were measured by radioimmunoassay and expression of protein and mRNA of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase in the perfused PCCSM were measured by western blot and real-time PCR, respectively. The interaction of ACE or scopoletin with udenafil was also evaluated. ACE and scopoletin exerted a significant and concentration-dependent relaxation in PCCSM. The perfusion with ACE or scopoletin significantly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and the perfusion with ACE or scopoletin increased the expression of eNOS mRNA and protein. Furthermore, ACE or scopoletin enhanced udenafil-inducing relaxation in PCCSM. ACE and scopoletin relaxed the PCCSM mainly by activating nitric oxide–cGMP system and cAMP pathway and they may be additive therapeutic candidates for ED patients who do not completely respond to udenafil.

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References

  1. Zhu YC, Zhao JL, Wu YG, Yuan YM, Lian WQ, Zhang J et al. Clinical features and treatment options for Chinese patients with severe primary erectile dysfunction. Urology 2010; 76: 387–390.

    Article  PubMed  Google Scholar 

  2. Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol 2010; 57: 804–814.

    Article  PubMed  Google Scholar 

  3. National Health and Nutrition Examination Survey. NHANES response rates and population totals (2003-2004). Available at: http://www.n.cdc.gov/nchs/nhanes/2003-2004/KIQ_P_C.htm#KIQ400. (accessed 24 April 2015).

  4. Deng W, Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ . Gene and stem cell therapy for erectile dysfunction. Int J Impot Res 2005; 17: S57–S63.

    Article  CAS  PubMed  Google Scholar 

  5. Chiou WF, Chen CF . Pharmacological profile of evodiamine in isolated rabbit corpus cavernosum. Eur J Pharmacol 2002; 446: 151–159.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang G, Liu Y, Ruoho AE, Hurley JH . Structure of the adenylyl cyclase catalytic core. Nature 1997; 386: 247–253.

    Article  CAS  PubMed  Google Scholar 

  7. Liu ZL, Chu SS, Liu QR . Chemical composition and insecticidal activity against Sitophilus zeamais of the essential oils of Artemisia capillaris and Artemisia mongolica. Molecules 2010; 15: 2600–2608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhao C, Kim HK, Kim SZ, Chae HJ, Cui WS, Lee SW et al. What is the role of unripe Rubus coreanus extract on penile erection? Phytother Res 2011; 25: 1046–1053.

    Article  PubMed  Google Scholar 

  9. Krause J, Tobi G, Marianna K . Using Old Solutions to New Problems - Natural Drug Discovery in the 21st Century Discovery Development, and Regulation of Natural Product. InTech:: Croatia, Europe, 2013, pp 5–9.

    Google Scholar 

  10. Kim EK, Kwon KB, Han MJ, Song MY, Lee JH, Lv N et al. Inhibitory effect of Artemisia capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells. Int J Mol Med 2007; 19: 535–540.

    PubMed  Google Scholar 

  11. Yamahara J, Kobayashi G, Matsuda H, Katayama T, Fujimura H . The effect of scoparone, a coumarin derivative isolated from the Chinese crude drug Artemisiae capillaris flos, on the heart. Chem Pharm Bull (Tokyo) 1989; 37: 1297–1299.

    Article  CAS  Google Scholar 

  12. Singh HP, Kaur S, Mittal S, Batish DR, Kohli RK . In vitro screening of essential oil from young and mature leaves of Artemisia scoparia compared to its major constituents for free radical scavenging activity. Food Chem Toxicol 2010; 48: 1040–1044.

    Article  CAS  PubMed  Google Scholar 

  13. Seo KS, Jeong HJ, Yun KW . Antimicrobial activity and chemical components of two plants, Artemisia capillaris and Artemisia iwayomogi, used as Korean herbal Injin. J Ecol Biol 2010; 33: 141–147.

    Google Scholar 

  14. Kim YS, Bahn KN, Hah CK, Gang HI, Ha YL . Inhibition of 7,12-dimethylbenz [a]anthracene induced mouse skin carcinogenesis by Artemisia capillaris. J Food Sci 2008; 73: T16–T20.

    Article  CAS  PubMed  Google Scholar 

  15. Yamahara J, Kobayashi G, Matsuda H, Katayama T, Fujimura H . Vascular dilatory action of Artemisia capillaris bud extracts and their active constituent. J Ethnopharmacol 1989; 26: 129–136.

    Article  CAS  PubMed  Google Scholar 

  16. Estrada-Soto S, Sanchez-Recillas A, Navarrete-Vazquez G, Castillo-Espana P, Villalobos-Molina R, Ibarra-Barajas M . Relaxant effects of Artemisia ludoviciana on isolated rat smooth muscle tissues. J Ethnopharmacol 2012; 139: 513–518.

    Article  PubMed  Google Scholar 

  17. Natividad GM, Broadley KJ, Kariuki B, Kidd EJ, Ford WR, Simons C . Actions of Artemisia vulgaris extracts and isolated sesquiterpene lactones against receptors mediating contraction of guinea pig ileum and trachea. J Ethnopharmacol 2011; 137: 808–816.

    Article  CAS  PubMed  Google Scholar 

  18. Aziz M, Karim A, El Ouariachi el M, Bouyanzer A, Amrani S, Mekhfi H et al. Relaxant effect of essential oil of Artemisia herba-alba Asso on rodent jejunum contractions. Sci Pharm 2012; 80: 457–467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. Calderone V, Martinotti E, Baragatti B, Breschi MC, Morelli I . Vascular effects of aqueous crude extracts of Artemisia verlotorum Lamotte (Compositae): in vivo and in vitro pharmacological studies in rats. Phytother Res 1999; 13: 645–648.

    Article  CAS  PubMed  Google Scholar 

  21. Christ GJ . The penis as a vascular organ. The importance of corporal smooth muscle tone in the control of erection. Urol Clin North Am 1995; 22: 727–745.

    CAS  PubMed  Google Scholar 

  22. Kwon OS, Choi JS, Islam MN, Kim YS, Kim HP . Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. Arch Pharm Res 2011; 34: 1561–1569.

    Article  CAS  PubMed  Google Scholar 

  23. Jung HA, Park JJ, Islam MN, Jin SE, Min BS, Lee JH et al. Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation. Arch Pharm Res 2012; 35: 1021–1035.

    Article  CAS  PubMed  Google Scholar 

  24. Hoult JR, Paya M . Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996; 27: 713–722.

    Article  CAS  PubMed  Google Scholar 

  25. Zhao C, Chae HJ, Kim SH, Cui WS, Lee SW, Jeon JH et al. A new perfusion model for studying erectile function. J Sex Med 2010; 7: 1419–1428.

    Article  PubMed  Google Scholar 

  26. Sung HH, Lee SW . Chronic low dosing of phosphodiesterase type 5 inhibitor for erectile dysfunction. Korean J Urol 2012; 53: 377–385.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA . Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med 1998; 338: 1397–1404.

    Article  CAS  PubMed  Google Scholar 

  28. Francis SH, Busch JL, Corbin JD, Sibley D . cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 2010; 62: 525–563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Beavo JA . Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 1995; 75: 725–748.

    Article  CAS  PubMed  Google Scholar 

  30. Sun K, Zhao C, Chen XF, Kim HK, Choi BR, Huang YR et al. Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus cavernosum. Asian J Androl 2013; 15: 134–137.

    Article  PubMed  Google Scholar 

  31. Wuyts WA, Vanaudenaerde BM, Dupont LJ, Demedts MG, Verleden GM . Modulation by cAMP of IL-1beta-induced eotaxin and MCP-1 expression and release in human airway smooth muscle cells. Eur Respir 2003; 22: 220–226.

    Article  CAS  Google Scholar 

  32. Cerqueira JB, Gonzaga-Silva LF, Silva FO, Cerqueira JV, Oliveira RR, Moraes ME et al. Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound. Int Braz J Urol 2012; 38: 687–694.

    Article  PubMed  Google Scholar 

  33. Kim HK, Choi BR, Bak YO, Zhao C, Lee SW, Jeon JH et al. The role of capillarisin from Artemisia capillaris on penile erection. Phytother Res 2012; 26: 800–805.

    Article  CAS  PubMed  Google Scholar 

  34. Kim HK, Park JK . The effect of Scoparone from Artemisia capillaris on the smooth muscle of rabbit penile corpus cavernosum. Kor J Clin Pharm 2011; 21: 1–5.

    Google Scholar 

  35. Klotz T, Bloch W, Zimmermann J, Ruth P, Engelmann U, Addicks K . Soluble guanylate cyclase and cGMP-dependent protein kinase I expression in the human corpus cavernosum. Int J Impot Res 2000; 12: 157–164.

    Article  CAS  PubMed  Google Scholar 

  36. Recio P, Lopez PG, Hernandez M, Prieto D, Contreras J, Garcia-Sacristan A . Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP. Eur J Pharmacol 1998; 351: 85–94.

    Article  CAS  PubMed  Google Scholar 

  37. Sciarra A, Voria G, Gentile V, Pastore AL, Di Chiro C, Loreto A et al. Role of nitric oxide in the urogenital system: physiology and pathology. Minerva Urol Nefrol 2000; 52: 201–206.

    CAS  PubMed  Google Scholar 

  38. Gonzalez-Cadavid NF, Ignarro LJ, Rajfer J . Nitric oxide and the cyclic GMP system in the penis. Mol Urol 1999; 3: 51–59.

    CAS  PubMed  Google Scholar 

  39. Burnett AL, Nelson RJ, Calvin DC, Liu JX, Demas GE, Klein SL et al. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase. Mol Med 1996; 2: 288–296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rand MJ, Li CG . Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol 1995; 57: 659–682.

    Article  CAS  PubMed  Google Scholar 

  41. Burnett AL . Erectile dysfunction. J Urol 2006; 175: S25–S31.

    PubMed  Google Scholar 

  42. Steers WD . Pharmacologic treatment of erectile dysfunction. Rev Urol 2002; 4: S17–S25.

    PubMed  PubMed Central  Google Scholar 

  43. Kirby M, Jackson G, Simonsen U . Endothelial dysfunction links erectile dysfunction to heart disease. Int J Clin Pract 2005; 59: 225–229.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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 and Welfare, Republic of Korea (HI13C0104). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Yun Ok Back for technical assistance.

Author contributions

BRC designed the experiments, analyzed the data and wrote the manuscript. CZ, LTZ and SKK performed western blotting study and treated animals. CYK performed plant extraction and isolation. SWL, J-HJ, IS, SHK and NCP contributed reagents, materials and analysis tools. HKK performed and designed the experiments, analyzed the data and wrote the manuscript. JKP directed the research project, analyzed the data and wrote the manuscript. All the authors have read and approved the final manuscript.

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Author notes

  1. H K Kim and J K Park: These authors contributed equally to this work.

Authors and Affiliations

  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, Republic of Korea

    B R Choi, S K Kumar, L T Zhang, H K Kim & J K Park

  2. Department of Urology, Renji Hospital, Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, China

    C Zhao

  3. Department of Pharmacognosy, Hangyang University, Ansan, Republic of Korea

    C Y Kim

  4. Department of Urology, Sungkyunkwan University Medical School, Seoul, Republic of Korea

    S W Lee

  5. Department of Physiology, Seoul National University Medical School, Seoul, Republic of Korea

    J-H Jeon & I So

  6. Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea

    S H Kim

  7. Department of Urology, Pusan National University Hospital, Busan, Republic of Korea

    N C Park

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Correspondence to H K Kim or J K Park.

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Choi, B., Kumar, S., Zhao, C. et al. Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle. Int J Impot Res 27, 225–232 (2015). https://doi.org/10.1038/ijir.2015.23

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