In vitro Erectogenic Property of Aqueous Extract from Roasted and Raw Pepitas in Isolated Corpora cavernosa of Wistar Rats
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Abstract
Pepitas have long been adopted in traditional medicine to to help with erectile dysfunction (ED) and cure impotence in males. This study investigated the inhibitory potentials of raw and roasted pepitas on some of the main enzymes associated with erectile dysfunction in the corpora cavernosa of rats. Arginase, Phosphodiesterase-5 (PDE-5), acetylcholinesterase (AChE), angiotensin I-conversion enzyme (ACE), and adenosine deaminase (ADA) were among the enzymes studied. The raw and roasted pepitas water extract (1:10 w/v) was employed. Gas chromatography-Pulsed Flame Photometric Detector (GC-PFPD) was also used to assess the amino acid content of roasted and raw pepitas. In the rat's corpora cavernosa, the roasted extract exhibited higher inhibitory activities for PDE-5 (IC50 = 15.76 g/mL), ACE (IC50 = 37.29 g/mL), AChE (IC50 = 28.34 g/mL), arginase (IC50 = 44.86 g/mL), and ADA (IC50 = 15.10 g/mL). The roasted extract had a lot of arginine, while the raw extract didn't have any. Pepitas' enzyme activity and erectogenic qualities might be linked to their amino acid contents. The pepitas that had been roasted seemed to be the most promising.
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References
Hatzimouratidis K, Amar E, Eardley I, Giuliano F, Hatzichristou D, Montorsi F, Vardi Y, Wespes E. European Association of Urology. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010; 57(5): 804-814.
Cheng JYW, Ng EML, Chen RYL, Ko JSN. Prevalence of erectile dysfunction in Asian populations: A meta-analysis. Int J Impot Res. 2007; 19(3):229–244.
He LJ, Zhang C, Li WY, Song GH, Jiang T, Geng F. Erectile function of male rats in different age groups: an experimental study. Zhonghua nan ke xue = Natl J Androl. 2013; 19(4):296–299.
Aytac IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999; 84:50 –56.
Giugliano F, Maiorino M, Bellastella G, Gicchino M, Giugliano D, Esposito K. Determinants of erectile dysfunction in Type-2 diabetes. Int J Impot Res. 2010; 22:204–209.
Goswami SK, Inamdar MN, Jamwal R, Dethe S. Effect of Cinnamomum cassia methanol extract and sildenafil on arginase and sexual function of young male Wistar rats. J Sex Med. 2014; 11:1475–483.
Vargas VM, Torres D, Corona F, Vergara M, Gomez LE, Delgado-Lezama R, Cueva-Rolon R. Cholinergic facilitation of erection and ejaculation in spinal cordtransected rats. Int J Impot Res. 2004: 16:86–90.
Akomolafe SF, Oboh G, Oyeleye SI, Boligon AA. Aqueous extract from Ficus capensis leaves inhibits key enzymes linked to erectile dysfunction and prevent oxidative stress in rats' penile tissue. NFS J. 2016a: 4:15–21.
Akomolafe SF, Oyeleye IS, Molehin OR, Ogunsuyi OB. Phenolic composition and inhibitory ability of methanolic extract from Pumpkin (Cucurbita pepo L.) seeds on Fe2+-induced thiobarbituric acid reactive species in albino rat’s testicular tissue - In Vitro. J Appl Pharm Sci. 2016b; 6(9):115 – 120.
Ojo OA, Ojo AB, Ajiboye BO, Oyinloye BE, Akinyemi AJ, Okesola MA, Boligon AA, de Campos MM. Chromatographic fingerprint analysis, antioxidant properties, and inhibition of cholinergic enzymes (acetylcholinesterase and butyrylcholinesterase) of phenolic extracts from Irvingia gabonensis (Aubry-Lecomte ex O’Rorke) Baill bark. J Basic Clinl Physiol Pharmacol. 2018a; 29(2):217–224.
Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011; 63:811–859.
Nunes KP and Webb RC. Mechanisms in Erectile Functionand Dysfunction: An Overview. Erectile Dysfunction -Disease-Associated Mechanisms and Novel Insights into Therapy, edited by Kenia Nunes, IntechOpen, 2012; 10.5772/39088.
Oboh G, Ademiluyi AO, Ademosun AO, Olasehinde TA, Oyeleye SI, Boligon AA, Athayde ML. Phenolic extract from Moringa oleifera leaves inhibits key enzymes linked to erectile dysfunction and oxidative stress in rats' penile tissues. Biochem Res Int. 2015: Article ID, 175950.
Mi T, Abbasi S, Zhang H, Uray K, Chunn JL, Xia LW, Xia Y. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Investig. 2008; 118:1491–1501.
Phatarpekar PV, Wen J, Xia Y. Role of adenosine signaling in penile erection and erectile disorders. J Sex Med. 2010; 7(11): 3553–3564.
Olabiyi AA, Oboh G, Akinyemi AJ, Ademiluyi AO, Boligon AA, Anraku de Campos MM. Tiger nut (Cyperus esculentus L.) supplemented diet modulate key biochemical indices relevant to erectile function in male rats. J Funct Foods. 2017; 34: 152–158.
Bader M. Tissue renin–angiotensin–aldosterone systems: targets for pharmacological therapy. Annu Rev Pharmacol Toxicol. 2010; 50:439–465.
Fraga-Silva RA, Montecucc F, Mach F, Santos RA, Stergiopulos N. Pathophysiological role of the renin–angiotensin system on erectile dysfunction. Eur J Clin Investig. 2013; 43:978–985.
Dorrance AM, Lewis RW, Mills TM, Mills TM. Captopril treatment reverses erectile dysfunction in male stroke prone spontaneously hypertensive rats. Int J Impot Res. 2002; 14:494–497.
Oloyede FM. Growth, yield and antioxidant profile of pumpkin (Cucurbita pepo L.) leafy vegetable as affected by NPK compound fertilizer. J Soil Sci Plant Nutr. 2012; 12(3):379-387.
Sarkar S and Guha D. Effect of ripe fruit pulp extract of Cucurbita pepo Linn. in aspirin induced gastric and duodenal ulcer in rats. Indian J Exp Biol. 2008; 46(9):639-645.
Pier GP, Giorgia M, Francesco G, Erica L, Ryszard A. Antioxidative activities and phenolic compounds of pumpkin (Cucurbita pepo) seeds and amaranth (Amaranthus caudatus) grain extracts. Nat Prod Res.2017; 31(18):2178-2182.
Bombardelli E and Morazoni P. Cucurbita pepo L. Fitoter. 1997; 68:291-302.
Oboh G, Puntel RL, Rocha JBT. Hot pepper (Capsicum annuum, tepin and Capsicum chinese, Habanero) prevents Fe2+
-induced lipid peroxidation in brain in vitro. Food Chem. 2007; 102:178-185.
Kaysen GH and Strecker HJ. Purification and properties of arginase of rat kidney. Biochem J. 1973; 133:779-788.
Cushman DW and Cheung HS. Spectrophotometric assay and properties of the Angiotensin I-converting enzyme of rabbit lung. Biochem Pharmacol. 1971; 20:1637-1648.
Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK. In vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer’s disease. J Pharmacol. 2003; 52:895–902.
Kelly SJ and Butler LG. Enzymatic hydrolysis of phosphonate esters: reaction mechanism of intestinal 5′-nucleotide phophodiesteras. Biochem. 1977; 16(6):1102-1104.
Giusti G and Gakis C. Temperature conversion factors, activation energy, relative substrate specificity and optimum pH of adenosine deaminase from human serum and tissues. Enzyme. 1971; 12:417-425.
AOAC. Official method of analysis. 18th edition, Asociation of Official Analytical Chemists, Gaithersburgs, MD. 2006.
Champion HC, Bivalacqua TJ, Hyman AL, Ignarro LJ, Hellstrom WJ, Kadowitz PJ. Gene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat. Proc Natl Acad Sci, USA. 1999; 96:11648-11652.
Kim SW, Cuong TD, Hung TM, Ryoo S, Lee JH, Min BS. Arginase II inhibitory activity of flavonoid compounds from Scutellaria indica. Archives Pharm Res. 2013; 36:922–929.
Segal R, Hannan JL, Liu X, Kutlu O, Burnett AL, Champion HC, Kim JH, Steppan D, Berkowitz DE, Bivalacqua TJ. Chronic Oral Administration of the Arginase Inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats. J Androl. 2012; 33:1169-1175.
Cassidy A, Franz M, Rimm EB. Dietary flavonoid intake and incidence of erectile dysfunction. Am J Clin Nutr. 2016; 106:534-541.
Jin L. Angiotensin II. Signaling and its implication in erectile dysfunction. J Sex Med 2009; 6(3):302–310.
Jung J, Jo HW, Kwon H, Jeong, NY. Clinical Neuroanatomy and Neurotransmitter-Mediated Regulation of Penile Erection. Int Neurourol J. 2014; 18:58-62.
Saenz de Tejada I, Blanco R, Goldstein I, Azadzoi K, de las Morenas A, Krane RJ, Cohen RA. Cholinergic neurotransmission in human corpus cavernosum: I. Responses to isolated tissue. Am J Physiol. 1988; 254:459–467.
Okamura T, Ayajiki K, Fujioka H, Toda M, Fujimiya M, Toda N. Effects of endothelial impairment by saponin on the responses to vasodilators and nitrergic nerve stimulation in isolated canine corpus cavernosum. Br J Pharmacol. 1999; 127:802–808.
Knispel HH, Goessl C, Beckmann R. Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous mooth muscle. J Urol. 1991; 146:1429–1433.
Azadzoi KM and Saenz de Tejada I. Diabetes mellitus impairs neurogenic and endothelium- dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol. 1992; 148:1587-1591.
Burnett AL, Chang AG, Crone JK, Huang PL, Sezen SF. Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase. J Androl. 2002; 23:92-97.
Cashen DE, MacIntyre DE, Martin WJ. Effects of sildenafil on erectile activity in mice lacking neuronal or endothelial nitric oxide synthase. Br J Pharmacol. 2002; 136: 693–700.
Kloner RA and Rezkalla SH. Cocaine and the Heart. N Engl J Med. 2003; 348(6):487-488.
Mi T, Abbasi S, Zhang H, Uray K, Chunn JL, Xia LW, Xia Y. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling. J Clin Investig. 2008; 118:1491-1501.
D'Aniello G, Tolino A, D'Aniello A, Errico F, Fisher GH, DiFoire MM. The Role of D-aspartic acid and N-methyl-Daspartic acid in the regulation of prolactin release. Endocrinol. 2000; 141:3862-3870.
Topo E, Soricelli A, D'Aniello A, Ronsini S, D'Aniello G. The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol. 2009; 7:120.
Boucher JL, Moali C, Tenu JP. Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization. Cell Mol Life Sci. 1999; 55:1015-1028.
Gur S, Ozturk B, Karahan ST. Impaired endotheliumdependent and neurogenic relaxation of corpus cavernosum from diabetic rats: improvement with L-arginine. Urology Resour. 2000; 28:14-19.
D'Aniello A. D-Aspartic acid: an endogenous amino acid with an important neuroendocrine role. Brain Res Revol. 2007; 53(2):215-234.
Schirar A, Bonnefond C, Meusnier C, Devinoy E. Androgens modulate nitric oxide synthase messenger ribonucleic acid expression in neurons of the major pelvic ganglion in the rat. Endocrinol. 1997; 138(8):3093-3102.
Ademiluyi AO, Oyeniran OH, Jimoh TO, Oboh G, Boligon AA. Fluted Pumpkin (Telfairia occidentalis) seed modulate markers of erectile function in isolated rat’s corpus cavernosum: Influence of polyphenol and amino acid constituents. J Food Biochem. 2019; 43(11):e13037.