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
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (33)
- Panossian A, "Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine", J Ethnopharmacol, 118, pp.183~212 (2008)[DOI]
- He XG, "Analysis of lignan constituents from Schisandra chinensis by liquid chromatography-electrospray mass spectrometry", J Chromatogr A, 757, pp.81~87 (1997)[DOI]
- Kim EY, "Cardioprotective effects of aqueous Schizandra chinensis fruit extract on ovariectomized and ballooninduced carotid artery injury rat models: effects on serum lipid profiles and blood pressure", J Ethnopharmacol, 134, pp.668~675 (2011)[DOI]
- Hikino H, "Antihepatotoxic actions of lignoids from Schizandra chinensis fruits", Planta Med, 50, pp.213~218 (1984)[DOI]
- Hu D, "Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates <TEX>$A{\beta}$<", TEX> 1-42-induced memory impairment in mice, 2012, 721721~
- Kang S, "Identification of a novel anti-inflammatory compound, <TEX>${\alpha}$<", TEX>-cubebenoate from Schisandra chinensis, 2014, pp.153, 242~249
- Han DH, "Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells", BJU Int, 109, pp.1404~1413 (2012)[DOI]
- Liu W, "Cavernosum smooth muscle relaxation induced by Schisandrol A via the NO-cGMP signaling pathway", Cell Mol Biol, 62, pp.115~119 (2016)
- Wespes E, "Guidelines on erectile dysfunction", Eur Urol, 41, pp.1~5 (2002)[DOI]
- 조유장, "가정의학과 의원 방문환자의 발기부전 유병률 및 성상담 진료 이용 현황과 관련 요소", Korean Journal of Family Medicine, 30(8), pp.617~625 (2009), 대한가정의학회
- 이재홍, "Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans", Journal of Periodontal & Implant Science, 47(2), pp.96~105 (2017), 대한치주과학회
- Ghalayini IF, "Nitric oxide-cyclic GMP pathway with some emphasis on cavernosal contractility", Int J Impot Res, 16, pp.459~469 (2004)[DOI]
- Paul V, "Involvement of nitric oxide in learning & memory processes", Indian J Med Res, 133, pp.471~478 (2011)
- Nunes KP, "Erectile Dysfunction: Disease-associated Mechanisms and Novel Insights into Therapy" (2012), InTech
- Toque HA, "New approaches to the design and discovery of therapies to prevent erectile dysfunction", Expert Opin Drug Discov, 9, pp.1447~1469 (2014)[DOI]
- Recio P, "Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP", Eur J Pharmacol, 351, pp.85~94 (1998)[DOI]
- Zhang G, "Structure of the adenylyl cyclase catalytic core", Nature, 386, pp.247~253 (1997)[DOI]
- Rhyu MR, "Aqueous extract of Schizandra chinensis fruit causes endothelium-dependent and-independent relaxation of isolated rat thoracic aorta", Phytomedicine, 13, pp.651~657 (2006)[DOI]
- Zhao C, "A new perfusion model for studying erectile function", J Sex Med, 7, pp.1419~1428 (2010)[DOI]
- Cui X, "Effects of pituitary adenylate cyclase activating polypeptide27 on cyclic AMP efflux and atrial dynamics in perfused beating atria", Eur J Pharmacol, 402, pp.129~137 (2000)[DOI]
- Kim HK, "The role of the lignan constituents in the effect of Schisandra chinensis fruit extract on penile erection", Phytother Res, 25, pp.1776~1782 (2011)[DOI]
- Seok YM, "Effects of gomisin A on vascular contraction in rat aortic rings", Naunyn Schmiedebergs Arch Pharmacol, 383, pp.45~56 (2011)[DOI]
- Park JY, "Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta", Planta Med, 73, pp.1537~1542 (2007)[DOI]
- McMahon CG, "Erectile dysfunction", Intern Med J, 44, pp.18~26 (2014)[DOI]
- Kandeel FR, "Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment", Endocr Rev, 22, pp.342~388 (2001)[DOI]
- Gonzalez-Cadavid NF, "The pleiotropic effects of inducible nitric oxide synthase (iNOS) on the physiology and pathology of penile erection", Curr Pharm Des, 11, pp.4041~4046 (2005)[DOI]
- Haas CA, "Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase", Urology, 51, pp.516~522 (1998)[DOI]
- Park JY, "The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta", J Ethnopharmacol, 121, pp.69~73 (2009)[DOI]
- Wespes E, "EAU guidelines on erectile dysfunction: an update", Eur Urol, 49, pp.806~815 (2006)[DOI]
- Huang SA, "Phosphodiesterase-5 (PDE5) inhibitors in the management of erectile dysfunction", P T, 38, pp.407~419 (2013)
- DeBusk RF, "Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease", Am J Cardiol, 93, pp.147~153 (2004)[DOI]
- Wachtel H, "Potential antidepressant activity of rolipram and other selective cyclic adenosine 3',5'-monophosphate phosphodiesterase inhibitors", Neuropharmacology, 22, pp.267~272 (1983)[DOI]
- Beavo JA, "Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms", Physiol Rev, 75, pp.725~748 (1995)[DOI]
