The Efficacy of Tribulus terrestris and Cumminum cyminium Against Sexual Dysfunction in Diabetic Male Rats

Article ID: e080622205710 Pages: 11

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Abstract

Aim: The aim of the study was to assess the efficacy of Tribulus terristeris and Cumminum cyminium in a standardized diabetic animal model for various pathological conditions of male sexual dysfunction (i.e., loss of libido, erectile dysfunction, and infertility) and compare these herbs with standard drugs.

Background: The prevalence of sexual dysfunction is about 40-45% in adult women, and 20-30% of adult men have sexual dysfunction. Sexual dysfunction is more common in men with diabetes compared to non-diabetic peers.

Objective: The objective of the study was to evaluate the therapeutic effect of Tribulus terrestris (TT) and Cumminum cyminium (CC) against sexual dysfunction in males with diabetes.

Methods: In-vivo animal models were utilized to find out Tribulus terristeris and Cumminum cyminium. Libido study: Sexually active male Wistar rats were divided into 5 groups, i.e., control, fluoxetine treated, fluoxetine with Tribulus terristeris, fluoxetine with Cumminum cyminium and fluoxetine with bupriprion. These rats were treated for 28 days by giving different drugs to different groups. Erection study: Male Wistar rats were divided into 5 groups (six in each group) i.e. control, diabetic rats, diabetic rats treated with Tribulus terristeris, diabetic rats treated with Cumminum cyminium and diabetic treated with insulin. The rat penile tissue was taken by scarifying the rats, and in-vitro contraction and relaxation were carried out in a two-chamber student organ bath. Sperm analysis: Sperm were collected from previously scarified rats in an erection study, and collected sperm were washed and counted (using Neubauer haemocytometer), and sperm motility was also studied.

Results: Cumminum cyminium showed the significant reversal of loss of desire caused by fluoxetine which was comparable to standard drug bupropion. Insulin and Tribulus terristeris treated diabetic group of rats showed the lowest capability to relax, indicating setting up of erectile dysfunction. Diabetic rats exhibited a significant reduction in sperm density, % sperm motility, and % sperm viability. Insulin and C. cyminium treated diabetic rats showed significant improvement in sperm density, % sperm motility and % sperm viability.

Conclusion: Tribulus terristeris at the dose of 100 mg/kg b.w was found to improve erectile function, whereas Cumminum cyminium at the dose of 150 mg/kg b.w was found to improve libido and sperm profile of fluoxetine treated rats.

Keywords: Sexual dysfunction, Cuminum cyminum, Tribulus terrestris, diabetic rats, in-vivo studies.

Graphical Abstract

[1]
Li M, Qu W, Wang Y, Wan H, Tian C. Hypoglycemic effect of saponin from Tribulus terrestris. Zhong Yao Cai 2002; 25(6): 420-2.
[PMID: 12583337]
[2]
Zhang SJ, Qu WJ, Zhong SY. Inhibitory effects of saponins from Tribulus terrestris on alpha-glucosidase in small intestines of rats. Zhongguo Zhongyao Zazhi 2006; 31(11): 910-3.
[PMID: 17048632]
[3]
El-Tantawy WH, Hassanin LA. Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: A comparative study with T. terrestris (Caltrop). Indian J Exp Biol 2007; 45(9): 785-90.
[4]
Adaikan PG. 17 Decline in testosterone: Relationship to libido and sexual dysfunction. J Men’s Health 2011; 8(S1): S103.
[http://dx.doi.org/10.1016/S1875-6867(11)60050-X]
[5]
Yakubu MT, Akanji MA, Oladiji AT. Male sexual dysfunction and methods used in assessing medicinal plants with aphrodisiac potentials. Pharmacogn Rev 2007; 1(1): 49-56.
[6]
Agarwal SG, Thappa RK, Dhar KL, Atal CK. Essential oils of the seeds of Bunium bulbocastanum, Carum gracile lindle and Cuminum cyminum. Ind Perfum 1979; 22: 164-5.
[7]
Agrawal S. Volatile oil constituents and wilt resistance in cumin (Cuminum cyminum L.). Curr Sci 1996; 71(3): 177-8.
[8]
Al-Qarawi AA. Stimulatory effect of the aqueous extract of Ruta chalepensis on the sex organs and hormones of male rats. J Appl Res 2005; 5(1): 206-11.
[9]
Chauhan PS, Satti NK, Suri KA, Amina M, Bani S. Stimulatory effects of Cuminum cyminum and flavonoid glycoside on Cyclosporine-A and restraint stress induced immune-suppression in Swiss albino mice. Chem Biol Interact 2010; 185(1): 66-72.
[http://dx.doi.org/10.1016/j.cbi.2010.02.016] [PMID: 20156427]
[10]
Indurwade NH, Kawtikwar PS, Kosalge SB, Janbandhie NV. Herbal plants with aphrodisiac activity. Indian Drugs 2005; 42(2): 67-72.
[11]
Jagtap AG, Patil PB. Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats. Food Chem Toxicol 2010; 48(8-9): 2030-6.
[http://dx.doi.org/10.1016/j.fct.2010.04.048] [PMID: 20451573]
[12]
Johri RK. Cuminum cyminum and Carum carvi: An update. Pharmacogn Rev 2011; 5(9): 63-72.
[http://dx.doi.org/10.4103/0973-7847.79101] [PMID: 22096320]
[13]
Kumar PA, Reddy PY, Srinivas PN, Reddy GB. Delay of diabetic cataract in rats by the antiglycating potential of cumin through modulation of α-crystallin chaperone activity. J Nutr Biochem 2009; 20(7): 553-62.
[http://dx.doi.org/10.1016/j.jnutbio.2008.05.015] [PMID: 18789666]
[14]
Malini T, Vanithakumari G. Estrogenic activity of Cuminum cyminum in rats. Indian J Exp Biol 1987; 25(7): 442-4.
[PMID: 2963791]
[15]
Ramachandran S, Sridhar Y, Sam S, et al. Phytomedicine: Aphrodisiac activity of Butea frondosa extract in male rats 2004. 11: 165
[16]
Reiter B, Lechner M, Lorbeer E. The fatty acid profiles–including petroselinic and cis‐vaccenic acid–of different Umbelliferae seed oils. Lipid/Fett 1998; 100(11): 498-502.
[17]
Shirke SS, Jadhav SR, Jagtap AG. Methanolic extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in rats. Exp Biol Med (Maywood) 2008; 233(11): 1403-10.
[http://dx.doi.org/10.3181/0803-RM-93] [PMID: 18824723]
[18]
Willatgamuwa SA, Platel K, Saraswathi G, Srinivasan K. Antidiabetic influence of dietary cumin seeds (Cuminum cyminum) in streptozotocin induced diabetic rats. Nutr Res 1998; 18(1): 131-42.
[http://dx.doi.org/10.1016/S0271-5317(97)00207-8]
[19]
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813-20.
[http://dx.doi.org/10.1038/414813a] [PMID: 11742414]
[20]
Esposito K, Giugliano F, Ciotola M, De Sio M, D’Armiento M, Giugliano D. Obesity and sexual dysfunction, male and female. Int J Impot Res 2008; 20(4): 358-65.
[http://dx.doi.org/10.1038/ijir.2008.9] [PMID: 18401349]
[21]
Thorve VS, Kshirsagar AD, Vyawahare NS, Joshi VS, Ingale KG, Mohite RJ. Diabetes-induced erectile dysfunction: Epidemiology, pathophysiology and management. J Diabetes Complications 2011; 25(2): 129-36.
[http://dx.doi.org/10.1016/j.jdiacomp.2010.03.003] [PMID: 20462773]
[22]
Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol 1995; 48(1): 25-32.
[http://dx.doi.org/10.1016/0378-8741(95)01279-M] [PMID: 8569244]
[23]
Ryan JG, Gajraj J. Erectile dysfunction and its association with metabolic syndrome and endothelial function among patients with type 2 diabetes mellitus. J Diabetes Complications 2012; 26(2): 141-7.
[http://dx.doi.org/10.1016/j.jdiacomp.2011.12.001] [PMID: 22437118]
[24]
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5): 1047-53.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[25]
Albersen M, Fandel TM, Ling G, et al. Stimulatory effect of aqueous extract of Ruta chalepensis on sex organs and hormones of male rats. J Appl Res 2005; 5: 206-11.
[26]
Elhaddad NS, Efkerine EM, Khatab HA, Eldurssi IS, Belkasem EM. Anti-mutagenic action of Ruta chalepensis against rat sperm cell abnormalities-induced by potassium bromate. Annu Res Rev Biol 2020; 41-51.
[http://dx.doi.org/10.9734/arrb/2020/v35i230187]
[27]
Albersen M, Fandel TM, Lin G, et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med 2010; 7(10): 3331-40.
[http://dx.doi.org/10.1111/j.1743-6109.2010.01875.x] [PMID: 20561166]
[28]
Aviv A, Shelef A, Weizman A. An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction. J Clin Psychiatry 2004; 65(1): 97-103.
[http://dx.doi.org/10.4088/JCP.v65n0117] [PMID: 14744177]
[29]
Ayta 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(1): 50-6.
[http://dx.doi.org/10.1046/j.1464-410x.1999.00142.x] [PMID: 10444124]
[30]
Azadzoi KM, Payton T, Krane RJ, Goldstein I. Effects of intracavernosal trazodone hydrochloride: Animal and human studies. J Urol 1990; 144(5): 1277-82.
[http://dx.doi.org/10.1016/S0022-5347(17)39719-7] [PMID: 1977931]
[31]
Bancroft J, Janssen E. The dual control model of male sexual response: A theoretical approach to centrally mediated erectile dysfunction. Neurosci Biobehav Rev 2000; 24(5): 571-9.
[http://dx.doi.org/10.1016/S0149-7634(00)00024-5] [PMID: 10880822]
[32]
Basar MM, Yildiz M, Söylemezoglu F, et al. Histopathological changes and nitric oxide synthase activity in corpus cavernosum from rats with neurogenic erectile dysfunction. BJU Int 1999; 83(1): 101-7.
[http://dx.doi.org/10.1046/j.1464-410x.1999.00884.x] [PMID: 10233461]
[33]
Brioni JD, Nakane M, Hsieh GC, Moreland RB, Kolasa T, Sullivan JP. Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction. Int J Impot Res 2002; 14(1): 8-14.
[http://dx.doi.org/10.1038/sj.ijir.3900801] [PMID: 11896472]
[34]
Carro-Juárez M, Cervantes E, Cervantes-Méndez M, Rodríguez-Manzo G. Aphrodisiac properties of Montanoa tomentosa aqueous crude extract in male rats. Pharmacol Biochem Behav 2004; 78(1): 129-34.
[http://dx.doi.org/10.1016/j.pbb.2004.03.001] [PMID: 15159142]
[35]
Riedner CE, Rhoden EL, Ribeiro EP, Fuchs SC. Central obesity is an independent predictor of erectile dysfunction in older men. J Urol 2006; 176(4 Pt 1): 1519-23.
[http://dx.doi.org/10.1016/j.juro.2006.06.049] [PMID: 16952671]
[36]
Chatterjee R, Kottaridis PD, Lees WR, Ralph DJ, Goldstone AH. Cavernosal arterial insufficiency and erectile dysfunction in recipients of high-dose chemotherapy and total body irradiation for multiple myeloma. Lancet 2000; 355(9212): 1335-6.
[http://dx.doi.org/10.1016/S0140-6736(00)02121-8] [PMID: 10776752]
[37]
Chung WS, Sohn JH, Park YY. Is obesity an underlying factor in erectile dysfunction? Eur Urol 1999; 36(1): 68-70.
[http://dx.doi.org/10.1159/000019929] [PMID: 10364658]
[38]
Cohen JS. Comparison of FDA reports of patient deaths associated with sildenafil and with injectable alprostadil. Ann Pharmacother 2001; 35(3): 285-8.
[http://dx.doi.org/10.1345/aph.10218] [PMID: 11261524]
[39]
Derby CA, Araujo AB, Johannes CB, Feldman HA, McKinlay JB. Measurement of erectile dysfunction in population-based studies: The use of a single question self-assessment in the Massachusetts Male Aging Study. Int J Impot Res 2000; 12(4): 197-204.
[http://dx.doi.org/10.1038/sj.ijir.3900542] [PMID: 11079360]
[40]
Dettori JR, Koepsell TD, Cummings P, Corman JM. Erectile dysfunction after a long-distance cycling event: Associations with bicycle characteristics. J Urol 2004; 172(2): 637-41.
[http://dx.doi.org/10.1097/01.ju.0000130749.37731.9f] [PMID: 15247750]
[41]
Fitch W III. Patient satisfaction using vacuum constriction device in the treatment of erectile dysfunction. South Med J 1990; 83(9) (Suppl.): 2S-85.
[http://dx.doi.org/10.1097/00007611-199009001-00339]
[42]
Gonzales GF, Gasco M, Córdova A, Chung A, Rubio J, Villegas L. Effect of Lepidium meyenii (Maca) on spermatogenesis in male rats acutely exposed to high altitude (4340 m). J Endocrinol 2004; 180(1): 87-95.
[http://dx.doi.org/10.1677/joe.0.1800087] [PMID: 14709147]
[43]
Gresser U, Gleiter CH. Erectile dysfunction: Comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil--review of the literature. Eur J Med Res 2002; 7(10): 435-46.
[PMID: 12435622]
[44]
Huang X, Li S, Hu L. Growth hormone deficiency and age-related erectile dysfunction. Zhonghua Nan Ke Xue 2004; 10(11): 867-9.
[PMID: 15595694]
[45]
Keltner NL, McAfee KM, Taylor CL. Mechanisms and treatments of SSRI-induced sexual dysfunction. Perspect Psychiatr Care 2002; 38(3): 111-6.
[http://dx.doi.org/10.1111/j.1744-6163.2002.tb00665.x] [PMID: 12385082]
[46]
McVary KT, Carrier S, Wessells H. Smoking and erectile dysfunction: Evidence based analysis. J Urol 2001; 166(5): 1624-32.
[http://dx.doi.org/10.1016/S0022-5347(05)65641-8] [PMID: 11586190]
[47]
Lin CS, Xin ZC, Wang Z, Lin G, Lue TF. Molecular Yin and Yang of erectile function and dysfunction. Asian J Androl 2008; 10(3): 433-40.
[http://dx.doi.org/10.1111/j.1745-7262.2008.00396.x] [PMID: 18385905]
[48]
Nantia EA, Moundipa PF, Monsees TK, Carreau S. Medicinal plants as potential male anti-infertility agents: A review. Basic Clin Androl 2009; 19(3): 148-58.
[http://dx.doi.org/10.1007/s12610-009-0030-2]
[49]
Hamdiken M, Bouhalit S, Kechrid Z. Effect of Ruta chalepensis on zinc, lipid profile and antioxidant levels in the blood and tissue of streptozotocin-induced diabetes in rats fed zinc-deficient diets. Can J Diabetes 2018; 42(4): 356-64.
[http://dx.doi.org/10.1016/j.jcjd.2017.08.239] [PMID: 29037571]
[50]
Albersen M, Shindel AW, Mwamukonda KB, Lue TF. The future is today: Emerging drugs for the treatment of erectile dysfunction. Expert Opin Emerg Drugs 2010; 15(3): 467-80.
[http://dx.doi.org/10.1517/14728214.2010.480973] [PMID: 20415601]
[51]
Burchardt M, Burchardt T, Baer L, et al. Hypertension is associated with severe erectile dysfunction. J Urol 2000; 164(4): 1188-91.
[http://dx.doi.org/10.1016/S0022-5347(05)67138-8] [PMID: 10992363]
[52]
Vega Matuszcyk J, Larsson K, Eriksson E. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol Biochem Behav 1998; 60(2): 527-32.
[http://dx.doi.org/10.1016/S0091-3057(98)00010-0] [PMID: 9632236]
[53]
Kamatenesi-Mugisha M, Oryem-Origa H. Traditional herbal remedies used in the management of sexual impotence and erectile dysfunction in western Uganda. Afr Health Sci 2005; 5(1): 40-9.
[PMID: 15843130]
[54]
Baldo O, Eardley I. Diagnosis and investigation of men with erectile dysfunction. J Mens Health Gend 2005; 2(1): 79-86.
[http://dx.doi.org/10.1016/j.jmhg.2005.01.005]
[55]
Rajasekaran M, White S, Baquir A, Wilkes N. Rho-kinase inhibition improves erectile function in aging male Brown-Norway rats. J Androl 2005; 26(2): 182-8.
[http://dx.doi.org/10.1002/j.1939-4640.2005.tb01084.x] [PMID: 15713824]
[56]
Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 1999; 11(6): 319-26.
[http://dx.doi.org/10.1038/sj.ijir.3900472] [PMID: 10637462]
[57]
Simonis LA, Borovets S, Van Driel MF, Ten Duis HJ, Mensink HJ. Erectile dysfunction due to a ‘hidden’ penis after pelvic trauma. Int J Impot Res 1999; 11(1): 53-5.
[http://dx.doi.org/10.1038/sj.ijir.3900362] [PMID: 10098955]
[58]
Sousa CM, Havt A, Santos CF, et al. The relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa. J Sex Med 2010; 7(11): 3610-9.
[http://dx.doi.org/10.1111/j.1743-6109.2009.01672.x] [PMID: 20102442]
[59]
Tsao CW, Lee SS, Meng E, et al. Penile blunt trauma induced veno-occlusive erectile dysfunction. Arch Androl 2004; 50(3): 151-4.
[http://dx.doi.org/10.1080/01485010490425539] [PMID: 15204680]
[60]
Venetikou MS, Lambou T, Gizani D. Hyperprolactinaemia due to hypothalamic-pituitary disease or drug-induced in patients with erectile dysfunction. Andrologia 2008; 40(4): 240-4.
[http://dx.doi.org/10.1111/j.1439-0272.2008.00850.x] [PMID: 18727734]
[61]
Mirone V, Imbimbo C, Bortolotti A, et al. Cigarette smoking as risk factor for erectile dysfunction: Results from an Italian epidemiological study. Eur Urol 2002; 41(3): 294-7.
[http://dx.doi.org/10.1016/S0302-2838(02)00005-2] [PMID: 12180231]
[62]
Waldinger MD, Olivier B. Animal models of premature and retarded ejaculation. World J Urol 2005; 23(2): 115-8.
[http://dx.doi.org/10.1007/s00345-004-0493-x] [PMID: 15940532]
[63]
Wilson SK, Carson CC, Cleves MA, Delk JR II. Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin. J Urol 1998; 159(5): 1537-9.
[http://dx.doi.org/10.1097/00005392-199805000-00034] [PMID: 9554349]
[64]
Miller TA. Diagnostic evaluation of erectile dysfunction. Am Fam Physician 2000; 61(1): 95-104, 109-110.
[PMID: 10643952]
[65]
Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA guideline. J Urol 2018; 200(3): 633-41.
[http://dx.doi.org/10.1016/j.juro.2018.05.004] [PMID: 29746858]
[66]
Kouidrat Y, Pizzol D, Cosco T, et al. High prevalence of erectile dysfunction in diabetes: A systematic review and meta-analysis of 145 studies. Diabet Med 2017; 34(9): 1185-92.
[http://dx.doi.org/10.1111/dme.13403] [PMID: 28722225]
[67]
Kessler A, Sollie S, Challacombe B, Briggs K, Van Hemelrijck M. The global prevalence of erectile dysfunction: A review. BJU Int 2019; 124(4): 587-99.
[http://dx.doi.org/10.1111/bju.14813] [PMID: 31267639]
[68]
Mitidieri E, Cirino G, d’Emmanuele di Villa Bianca R, Sorrentino R. Pharmacology and perspectives in erectile dysfunction in man. Pharmacol Ther 2020; 208: 107493.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107493] [PMID: 31991196]
[69]
Hackett G, Kirby M, Wylie K, et al. British society for sexual medicine guidelines on the management of erectile dysfunction in men-2017. J Sex Med 2018; 15(4): 430-57.
[http://dx.doi.org/10.1016/j.jsxm.2018.01.023] [PMID: 29550461]
[70]
Nguyen HMT, Gabrielson AT, Hellstrom WJG. Erectile dysfunction in young men-a review of the prevalence and risk factors. Sex Med Rev 2017; 5(4): 508-20.
[http://dx.doi.org/10.1016/j.sxmr.2017.05.004] [PMID: 28642047]
[71]
Mobley DF, Khera M, Baum N. Recent advances in the treatment of erectile dysfunction. Postgrad Med J 2017; 93(1105): 679-85.
[http://dx.doi.org/10.1136/postgradmedj-2016-134073] [PMID: 28751439]
[72]
Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ. The serendipitous story of sildenafil: An unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019; 7(1): 115-28.
[http://dx.doi.org/10.1016/j.sxmr.2018.06.005] [PMID: 30301707]
[73]
Allen MS, Walter EE. Erectile dysfunction: An umbrella review of meta-analyses of risk-factors, treatment, and prevalence outcomes. J Sex Med 2019; 16(4): 531-41.
[http://dx.doi.org/10.1016/j.jsxm.2019.01.314] [PMID: 30833150]
[74]
Matz EL, Terlecki R, Zhang Y, Jackson J, Atala A. Stem cell therapy for erectile dysfunction. Sex Med Rev 2019; 7(2): 321-8.
[http://dx.doi.org/10.1016/j.sxmr.2017.12.008] [PMID: 29631980]