Toxicological Research

  • 제37권2호
  • /
  • Pages.249-260
  • /
  • 2021
  • /
  • 1976-8257(pISSN)
  • /
  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
권호 표지
DOI QR코드

DOI QR Code

β-caryophyllene improves sexual performance via modulation of crucial enzymes relevant to erectile dysfunction in rats

  • Adefegha, Stephen A. (Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology) ;
  • Oboh, Ganiyu (Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology) ;
  • Olopade, Elijah O. (Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology)
  • 투고 : 2020.04.28
  • 심사 : 2020.07.27
  • 발행 : 2021.04.15
⟨ 이전 논문 다음 논문 ⟩

초록

This study sought to investigate the effect of β-caryophyllene (BCP) on sexual performance, crucial enzymes linked to erectile function as well as lipid peroxidation in the penile tissue of paroxetine (PD)-induced rats. Animals were randomly divided into ten groups of five animals each: normal control (NC), BCP (10 mg/kg), BCP (20 mg/kg), sildenafil citrate (SD) (20 mg/kg), BCP+SD (20 mg/kg), PD (20 mg/kg), PD+BCP (10 mg/kg), PD+BCP (20 mg/kg), PD+SD (20 mg/kg) and PD+BCP (20 mg/kg)+SD (20 mg/kg). Oral administration of 20 mg/kg body weight of PD for the first 7 days was done while treatment with BCP and SD were performed between 8 and 14 days prior to euthanasia. The sexual performance study revealed that PD caused erectile dysfuction. Elevated activities of phosphodiesterase-5' (PDE-5'), arginase, adenosine deaminase (ADA), acetylcholinesterase (AChE) and angiotensin-I converting enzyme (ACE) as well as lipid peroxidation level were observed in PD-induced rats when compared to the NC group. However, treatment with sildenafil and/ or β-Caryophyllene significantly reduced the activities of AChE, PDE-5', arginase, ADA, and ACE in penile tissues of PD-induced rats. In addition, co-administration of β-caryophyllene and sildenafil citrate showed better modulatory effects. Thus, β-caryophyllene could represent a potential nutraceutical in the management of erectile dysfunction.

키워드

참고문헌

  1. Biri TH, Onaran M et al (2003) Cavernosal tissue nitrite, nitrate, malondialdehyde and glutathione levels in diabetic and non-diabetic erectile dysfunction. Int J Androl 26:250-254 https://doi.org/10.1046/j.1365-2605.2003.00427.x
  2. Dean RC, Lue TF (2005) Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am 32:379-395 https://doi.org/10.1016/j.ucl.2005.08.007
  3. Bivalacqua TJ, Usta MF, Champion HC et al (2003) Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl 24:S17-S37. https://doi.org/10.1002/j.1939-4640.2003.tb02743.x
  4. Silva FH, Veiga FJR, Mora AG et al (2017) A novel experimental model of erectile dysfunction in rats with heart failure using volume overload. PLoS ONE 12:0187083
  5. Werneke U, Northey S, Bhugra D (2006) Antidepressants and sexual dysfunction. Acta Psychiatr Scand 114:384-397 https://doi.org/10.1111/j.1600-0447.2006.00890.x
  6. Rajfer J, Aronson WJ, Bush PA et al (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission, New England. J Med Surg Collat Branches Sci 326:90-94
  7. Tostes RC, Giachini FR, Carneiro FS et al (2007) Determination of adenosine effects and adenosine receptors in murine corpus cavernosum. J Pharm Exp Ther 322:678-685 https://doi.org/10.1124/jpet.107.122705
  8. Yang R, Wang J, Chen Y et al (2008) Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats. J Androl 29:586-591 https://doi.org/10.2164/jandrol.107.004721
  9. Huang SA, Lie JD (2013) Phosphodiesterase-5 (PDE5) inhibitors in the management of erectile dysfunction. Pharm Ther 38(7):407-419
  10. Naylor AM (1998) Endogenous neurotransmitters mediating penile erection. Br J Urol 81:424-431 https://doi.org/10.1046/j.1464-410x.1998.00553.x
  11. Phatarpekar PV, Wen J, Xia Y (2010) Role of adenosine signaling in penile erection and erectile disorders. J Sex Med 7:3553-3564 https://doi.org/10.1111/j.1743-6109.2009.01555.x
  12. Adefegha SA, Oboh G, Oyeleye SI et al (2017) Erectogenic, antihypertensive, antidiabetic, anti-oxidative properties and phenolic compositions of almond fruit (Terminalia catappa L.) parts (hull and drupe)-in vitro. J Food Biochem 41:e12309 https://doi.org/10.1111/jfbc.12309
  13. Adefegha SA, Oboh G, Maduka BO et al (2017) Comparative effects of alkaloid extracts from Alligator pepper (Aframomum melegueta) and Bastered melegueta (Aframomum danielli) on enzymes relevant to erectile dysfunction. J Diet Suppl 14:542-552 https://doi.org/10.1080/19390211.2016.1272661
  14. Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M, Zimmer A (2008) Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci USA 105:9099-9104 https://doi.org/10.1073/pnas.0803601105
  15. Calleja MA, Vieites JM, Montero-Melendez T, Torres MI, Faus MJ, Gil A, Suarez A (2013) The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr 109:394-401 https://doi.org/10.1017/S0007114512001298
  16. Klauke AL, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J, Zimmer A (2014) The cannabinoid CB2 receptor-selective phytocannabinoid beta caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol 24:608-620 https://doi.org/10.1016/j.euroneuro.2013.10.008
  17. Dahham SS, Tabana YM, Iqbal MA, Ahamed MB, Ezzat MO, Majid AS, Majid AM (2015) The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-caryophyllene from the essential oil of Aquilaria crassna. Molecules 20:11808-11829 https://doi.org/10.3390/molecules200711808
  18. Agarwal RB, Rangari VD (2003) Phytochemical investigation and evaluation of anti-inflammatory and anti-arthritic activities of essential oil of Strobilanthus ixiocephala Benth. Indian J Exp Biol 41:890-894
  19. Younis NS, Mohamed ME (2019) β-Caryophyllene as a potential protective agent against myocardial injury: the role of toll-like receptors. Molecules 24:1929. https://doi.org/10.3390/molecules24101929
  20. Charu S, Juma MA, Syed MN, Sameer NG, Mohammad AK, Shreesh O (2016) Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des 22:1-28
  21. He J, Zhou S, Li X, Wang C, Yu Y, Chen X, Lu Y (2017) Pharmacokinetic evaluation of β-caryophyllene alcohol in rats and beagle dogs. Xenobiotica 48:845-850 https://doi.org/10.1080/00498254.2017.1367441
  22. Adefegha SA, Oyeleye SI, Dada FA, Olasehinde TA, Oboh G (2018) Modulatory effect of quercetin and its glycosylated form on key enzymes and antioxidant status in rats' penile tissue of paroxetine-induced erectile dysfunction. Biomed Pharmacother 107:1473-1479 https://doi.org/10.1016/j.biopha.2018.08.128
  23. Thawatchai P, Jintanaporn W, Sitthachai I, Supaporn M, Wipawee T (2012) Moringa olifera leaves extract attenuates male sexual dysfunction. Am J Neurosci 3:17-24 https://doi.org/10.3844/amjnsp.2012.17.24
  24. Ferraz MMD, Quntella SL, Parcial ALN, Ferraz MR (2016) The effects of sildenafil after chronic L-NAME administration in male rat sexual behaviour. Pharmacol Biochem Behav 146:13-20 https://doi.org/10.1016/j.pbb.2016.04.004
  25. Perry NS, Bollen C, Perry EK et al (2003) Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 75:651-659 https://doi.org/10.1016/S0091-3057(03)00108-4
  26. Kelly SJ, Butler LG (1977) Enzymic hydrolysis of phosphonateesters. Reaction mechanism of intestinal 50-nucleotide phosphodiesterase. Biochemistry 16:1102-1104 https://doi.org/10.1021/bi00625a011
  27. Zhang C, Hein TW, Wang W et al (2001) Constitutive expression of arginase in microvascular endothelial cells counteracts nitric oxide-mediated vasodilatory function. FASEB J 15:1264-1266 https://doi.org/10.1096/fj.00-0681fje
  28. Guisti G, Galanti B (1984) Colorimetric method. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie, Weinheim, pp 315-323
  29. Cushman DW, Cheung HS (1971) Spectrophotometric assay and properties of the Angiotensin I converting enzyme of rabbit lung. Biochem Pharmacol 20:1637-1648 https://doi.org/10.1016/0006-2952(71)90292-9
  30. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351-358 https://doi.org/10.1016/0003-2697(79)90738-3
  31. Andersson KE (2011) Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev 63:811-859 https://doi.org/10.1124/pr.111.004515
  32. Montejo-Gonzales AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A (1997) SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 23:176-194 https://doi.org/10.1080/00926239708403923
  33. Osis L, Bishop JR (2010) Pharmacogenetics of SSRIs and sexual dysfunction. Pharmaceuticals 3:3614-3628 https://doi.org/10.3390/ph3123614
  34. Higgins A, Nash M, Lynch AM (2010) Antidepressant-associated sexual dysfunction: impact, effects, and treatment. Drug Healthc Patient Saf 2:141-150 https://doi.org/10.2147/DHPS.S7634
  35. Burnett AL (2008) Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health. J Androl 29:3-14 https://doi.org/10.2164/jandrol.107.003483
  36. Jung J, Jo HW, Kwon H, Jeong NY (2014) Clinical neuroanatomy and neurotransmitter-mediated regulation of penile erection. Int Neurourol J 18:58-62 https://doi.org/10.5213/inj.2014.18.2.58
  37. Adefegha SA, Oyeleye SI, Oboh G (2018) African crocus (Curculigo pilosa) and Wonderful kola (Buchholzia coracea) seeds modulate critical enzymes relevant to erectile dysfunction and oxidative stress. J Complement Integr Med 15(4). https://doi.org/10.1515/jcim-2016-0159
  38. Outhoff K (2009) Antidepressant-induced sexual dysfunction. South Afr Fam Pract 51:298-302 https://doi.org/10.1080/20786204.2009.10873868
  39. Yakubu MT, Akanji M, Oladiji AT (2007) Male sexual dysfunction and method used in assessing medical plant with aphrodisiac potential. Pharmacogn Rev 1:49-56
  40. Adefegha SA, Oboh G, Oyeleye SI, Ejakpovi I (2016) Erectogenic, antihypertensive, antidiabetic, antioxidative properties and phenolic compositions of Almond Fruit (Terminalia catappa L.) Parts (Hull and Drupe)-in vitro. J Food Biochem 41:e12309 https://doi.org/10.1111/jfbc.12309
  41. Halliwell B (2007) Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc Res 73:341-347 https://doi.org/10.1016/j.cardiores.2006.10.004
  42. Scalbert A, Manach C, Morand C et al (2005) Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 45:287-306 https://doi.org/10.1080/1040869059096
  43. Eleazu C, Obianuju N, Eleazu K, Kalu W (2017) The role of dietary polyphenols in the management of erectile dysfunction-mechanisms of action. Biomed Pharmacother 88:644-652 https://doi.org/10.1016/j.biopha.2017.01.125
  44. Baldwin DS, Palazzo MC, Masdrakis VG (2013) Reduced treatment-emergent sexual dysfunction as a potential target in the development of new antidepressants. Depress Res Treat 25:68-41
  45. Corbin JD (2004) Mechanisms of action of PDE5 inhibition in erectile dysfunction. Int J Impot Res 16(Suppl 1):S4-S7. https://doi.org/10.1038/sj.ijir.3901205
  46. Kenia P, Clinton N (2012) Mechanisms in erectile function and dysfunction: an overview, erectile dysfunction. Disease-Associated Mechanisms and Novel Insights into Therapy, pp 1-22
  47. Michl U, Molfenter F, Graefen M et al (2015) Use of phosphodiesterase type 5 inhibitors may adversely impact biochemical recurrence after radical prostatectomy. J Urol 193:479-483 https://doi.org/10.1016/j.juro.2014.08.111
  48. Olabiyi AA, Oboh G, Adefegha SA (2017) Effect of dietary supplementation of tiger nut (Cyperus esculentus L.) and walnut (Tetracarpidium conophorum mull. Arg.) on sexual behavior, hormonal level, and antioxidant status in male rats. J Food Biochem 41:e12351 https://doi.org/10.1111/jfbc.12351
  49. Sebastiao AM, Ribeiro JA (2000) Fine-tuning neuromodulation by adenosine. Trends Pharmacol Sci 21:341-346 https://doi.org/10.1016/S0165-6147(00)01517-0
  50. Leal CAM, Leal DBR, Adefegha SA et al (2016) Effects of chlorogenic acid on adenine nucleotides hydrolyzing enzyme activities and expression in platelets of rats experimentally demyelinated with ethidium bromide. Biomed Pharmacother 81:363-370 https://doi.org/10.1016/j.biopha.2016.04.003
  51. Li G, Nakagome I, Hirono S et al (2015) Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances. Pharmacol Res Persp 3:e00121
  52. Fraga-Silva RA, Montecucco F, Mach F (2013) Pathophysiological role of the renin-angiotensin system on erectile dysfunction. Eur J Clin Invest 43:978-985 https://doi.org/10.1111/eci.12117
  53. Park JK, Kim SZ, Kim SH et al (1997) Renin angiotensin system in rabbit corpus cavernosum: functional characterization of angiotensin II receptors. J Urol 158:653-658 https://doi.org/10.1016/S0022-5347(01)64577-4
  54. Jin LM (2009) Angiotensin II signaling and its implication in erectile dysfunction. J Sex Med 6:302-310 https://doi.org/10.1111/j.1743-6109.2008.01188.x
  55. Agarwal A, Nandipati KC, Sharma RK et al (2006) Role of oxidative stress in the pathophysiological mechanism of erectile dysfunction. J Peritoneum 27:335-347
  56. Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normalphysiological functions and human disease. Int J Biochem Cell Biol 39:44-84 https://doi.org/10.1016/j.biocel.2006.07.001

피인용 문헌

  1. Berberine modulates crucial erectogenic biomolecules and alters histological architecture in penile tissues of diabetic rats vol.53, pp.7, 2021, https://doi.org/10.1111/and.14074