Home | About us | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Reviews
Search Article 
Advanced search 

 Table of Contents  
Year : 2014  |  Volume : 8  |  Issue : 16  |  Page : 113-121  

Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants

Department of Zoology, Center for Advanced Studies, University of Rajasthan, Jaipur, Rajasthan, India

Date of Submission19-Mar-2014
Date of Acceptance27-Mar-2014
Date of Web Publication10-Jun-2014

Correspondence Address:
Gyan Chand Jain
Department of Zoology, Center for Advanced Studies, University of Rajasthan, Jaipur 302 004, Rajasthan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-7847.134245

Rights and Permissions

Today diabetes mellitus has emerged as a major healthcare problem throughout the world. It has recently broken the age barrier and has been diagnosed in younger people also. Sustained hyperglycemia is associated with many complications including male reproductive dysfunctions and infertility. Numerous medicinal plants have been used for the management of the diabetes mellitus in various traditional system of medicine and in folklore worldwide as they are a rich source of bioactive phytoconstituents, which lower blood glucose level and/or also act as antioxidants resulting in the amelioration of oxidative-stress-induced diabetic complications. The present review describes the ameliorative effects of medicinal plants or their products, especially on male reproductive dysfunctions, in experimental diabetic animal models.

Keywords: Antioxidant, blood glucose, sperm function, testosterone, testis

How to cite this article:
Jain GC, Jangir RN. Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants. Phcog Rev 2014;8:113-21

How to cite this URL:
Jain GC, Jangir RN. Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants. Phcog Rev [serial online] 2014 [cited 2018 Oct 23];8:113-21. Available from: http://www.phcogrev.com/text.asp?2014/8/16/113/134245

   Introduction Top

Diabetes mellitus (DM) is a chronic, complicated metabolic disorder characterized by hyperglycemia, which often results from defects in insulin secretion, insulin action, or both. Moreover, DM is associated with severe disturbances of carbohydrate, fat, and protein metabolism. [1]

Diabetes is rapidly emerging as a major public health challenge and demands special attention towards its management. According to the diabetic  Atlas More Details of the International Diabetic Federation, 366 million people were affected by diabetes worldwide in 2011, and diabetes prevalence is expected to 522 million by 2030. [2] Furthermore, the increasing prevalence of diabetes mellitus in children and adolescents is also of concern. Poorly managed diabetes can lead to a large number of complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases, and male impotency. [3],[4]

A large number of studies, both in diabetic men and animal models indicate that DM causes male infertility based on impotency, retrograde ejaculation, and hypogonadism. DM may affect male reproductive functions at multiple levels including variation in sperm quality, altered spermatogenesis, morphological changes in testes, altered glucose metabolism in Sertoli-blood testes barrier, reduced testosterone, ejaculatory dysfunction, and reduced libido. [5],[6],[7],[8],[9],[10],[11],[12],[13] Several clinical and animal studies have focused on the molecular mechanism responsible for the alterations induced by DM in male reproductive potential including endocrine disorders, neuropathy, and increased oxidative stress. [12]

DM-induced adverse effects on male reproductive functions might be mediated through hormonal alterations in the hypothalamic-pituitary-gonadal axis or through the direct interactions of insulin with the testes and sperm cells, as both the testes and sperms themselves produce insulin. [11] Insulin expression in the testes also seems to be affected by diabetes. [14] Both diabetic men and knockout mice had notably impaired spermatogenesis, increased germ cell depletion, and Sertoli cell vacuolization, suggesting that insulin may have an important role in spermatogenesis. [6],[15] It is still unclear whether the effects of diabetes on male fertility are mediated through testicular insulin insufficiency or through systemic effects of diabetes. [16],[17],[18]

Furthermore, oxidative stress may play a pathogenic role in diabetes-related male reproductive function abnormalities. [12] Studies have shown that men suffering from diabetes have sperms with greater DNA fragmentation and an increase in advanced glycation end products and their receptors (RAGE) leading to deterioration of sperm quality, sperm functions coupled with changes in testicular metabolite levels and spermatogenic gene expression. [19],[20],[21] Several studies have shown that antioxidant treatment improves glycemic index, reduces diabetic complications, and protects components from oxidative damage. [22],[23]

The use of plants in the management of diabetes is well documented, which is primarily due to anti-hyperglycemic and/or oxygen radical scavenging of their various phytoconstituents through various mechanisms. [24],[25] Medicinal plants provide better alternatives as they are less toxic, easily available and affordable. [26]

A brief review of the medicinal plants having ameliorative effects on blood sugar levels and/or male reproductive functions in experimental diabetic animals is presented in [Table 1].
Table 1: Review of the literature of various plants/herbs showing modulatory effect on reproductive dysfunctions in male diabetic animals

Click here to view

   Conclusion Top

From the results of the above studies, it can be concluded that supplementation of medicinal plant products, extracts, or herbal formulations may be useful in alleviation of DM-induced complications, especially male reproductive dysfunction, by virtue of their antidiabetic, antioxidant, and androgenic activities of various bioactive phytoconstituents.[62]

   Acknowledgements Top

The authors are thankful to Professor N. P. Singh, Head of the Department and Center for Advanced Studies Phase II, Department of Zoology, University of Rajasthan, Jaipur for providing necessary facilities.

   References Top

1.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2011;34 Suppl 1:62-9.  Back to cited text no. 1
2.Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21.  Back to cited text no. 2
3.Melendez-Ramirez LY, Richards RJ, Cefalu WT. Complications of type 1 diabetes. Endocrinol Metab Clin North Am 2010;39:625-40.  Back to cited text no. 3
4.Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med 1994;331:1428-36.  Back to cited text no. 4
5.Sexton WJ, Jarow JP. Effect of diabetes mellitus upon male reproductive function. Urology 1997;49:508-13.  Back to cited text no. 5
6.Baccetti B, La Marca A, Piomboni P, Capitani S, Bruni E, Petraglia F, et al. Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality. Hum Reprod 2002;17:2673-7.  Back to cited text no. 6
7.Scarano WR, Messias AG, Oliva SU, Klinefelter GR, Kempinas WG. Sexual behaviour, sperm quantity and quality after short-term streptozotocin-induced hyperglycaemia in rats. Int J Androl 2006;29:482-8.  Back to cited text no. 7
8.Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, et al. Insulin dependent diabetes mellitus: Mplications for male reproductive function. Hum Reprod 2007;22:1871-7.  Back to cited text no. 8
9.Ricci G, Catizone A, Esposito R, Pisanti FA, Vietri MT, Galdieri M. Diabetic rat testes: Morphological and functional alterations. Andrologia 2009;41:361-8.  Back to cited text no. 9
10.Mallidis C, Agbaje I, McClure N, Kliesch S. The influence of diabetes mellitus on male reproductive function: A poorly investigated aspect of male infertility. Urologe A 2011;50:33-7.  Back to cited text no. 10
11.Schoeller EL, Schon S, Moley KH. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis. Cell Tissue Res 2012;349:839-47.  Back to cited text no. 11
12.La Vignera S, Condorelli R, Vicari E, D'Agata R, Calogero AE. Diabetes mellitus and sperm parameters. J Androl 2012;33:145-53.  Back to cited text no. 12
13.Alves MG, Martins AD, Cavaco JE, Socorro S, Oliveira PF. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function. Tissue Barriers 2013;1:e23992.  Back to cited text no. 13
14.Gomez O, Ballester B, Romero A, Arnal E, Almansa I, Miranda M, et al. Expression and regulation of insulin and the glucose transporter GLUT8 in the testes of diabetic rats. Horm Metab Res 2009;41:343-9.  Back to cited text no. 14
15.Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289:2122-5.  Back to cited text no. 15
16.Guneli E, Tugyan K, Ozturk H, Gumustekin M, Cilaker S, Uysal N. Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats. Eur Surg Res 2008;40:354-60.  Back to cited text no. 16
17.Rabbani SI, Devi K, Khanam S. Inhibitory effect of glimepiride on nicotinamide-streptozotocin induced nuclear damages and sperm abnormality in diabetic Wistar rats. Indian J Exp Biol 2009;47:804-10.  Back to cited text no. 17
18.Fernandes GS, Fernandez CD, Campos KE, Damasceno DC, Anselmo-Franci JA, Kempinas WD. Vitamin C partially attenuates male reproductive deficits in hyperglycemic rats. Reprod Biol Endocrinol 2011;9:100. Available from: http://www.rbej.com/content/9/1/100 [Last accessed on 2011 Oct 03].  Back to cited text no. 18
19.Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and impairment of reproductive function: Possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008;4:46-54.  Back to cited text no. 19
20.Mallidis C, Agbaje IM, Rogers DA, Glenn JV, Pringle R, Atkinson AB, et al. Advanced glycation end products accumulate in the reproductive tract of men with diabetes. Int J Androl 2009;32:295-305.  Back to cited text no. 20
21.Karimi J, Goodarzi MT, Tavilani H, Khodadadi I, Amiri I. Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men. Diabetes Res Clin Pract 2011;91:61-6.  Back to cited text no. 21
22.Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005;59:365-73.  Back to cited text no. 22
23.Mohasseb M, Ebied S, Yehia MA, Hussein N. Testicular oxidative damage and role of combined antioxidant supplementation in experimental diabetic rats. J Physiol Biochem 2011;67:185-94.  Back to cited text no. 23
24.Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol 2002;81:81-100.  Back to cited text no. 24
25.Chan CH, Ngoh GC, Yusoff R. A brief review on anti diabetic plants: Global distribution, active ingredients, extraction techniques and acting mechanisms. Pharmacogn Rev 2012;6:22-8.  Back to cited text no. 25
26.Khan V, Najmi AK, Akhtar M, Aqil M, Mujeeb M, Pillai KK. A pharmacological appraisal of medicinal plants with antidiabetic potential. J Pharm Bioallied Sci 2012;4:27-42.  Back to cited text no. 26
27.Luangpirom A, Kourchampa W, Junaimuang T, Somsapt P, Sritragool O. Effect of shallot (Allium ascalonicum L.) bulb juice on hypoglycemia and sperm quality in streptozotocin induced diabetic mice. ABAH Bioflux2013;5:49-54.  Back to cited text no. 27
28.Gholamhosini B, Khaki A, Ahmadi-Ashtiani HR, Rezazadeh S, Rastegar H, Fathiazad F, et al. Treatment effects of onion on spermatogenesis in streptozotocin-induced diabetic rat. J Med Plants 2009;8:153-61.  Back to cited text no. 28
29.Abdolahnejad A, Gol A, Dabiri S. Garlic effects on reproductive complications of diabetes mellitus in male rats. Physiol Pharmacol 2009;13:297-307.  Back to cited text no. 29
30.Sangameswaran B, Jayakar B. Anti-diabetic, anti-hyperlipidemic and spermatogenic effects of Amaranthus spinosus Linn. on streptozotocin-induced diabetic rats. J Nat Med 2008;62:79-82.  Back to cited text no. 30
31.Thakur M, Bhargava S, Dixit VK. Effect of Asparagus racemosus on sexual dysfunction in hyperglycemic male rats. Pharmaceut Biol 2009;47:390-5.  Back to cited text no. 31
32.Jassem HM, Ismaiel HK, Jasem AY. Effect of aqueous extract of green tea on sexual efficiency in adult male rats treated with alloxan. Iraq J Vet Sci 2008;22:75-82.  Back to cited text no. 32
33.Vyawahare NS, Kagathara VG, Kshirsagar AD, Rajendran R, Patil MN, Jagtap AA, et al. Effect of hydroalcoholic extract of Chlorophytum borivilianum tubers in alleviating the diabetic impotency in streptozotocin induced male diabetic rats. Phcog Res 2009;1:314-9.  Back to cited text no. 33
  Medknow Journal  
34.Hafez DA. Effect of extracts of ginger roots and Cinnamon bark on fertility of male diabetic rats. J Am Sc 2010;6:940-7.  Back to cited text no. 34
35.Khaki A, Ouladsahebmadarek E, Zahedi A, Ahmadnezhad B. Effect of water melon seeds extracts (citrullus vulgaris) on sperms in diabetic rat. Indones J Pharm 2013;24:122-6.  Back to cited text no. 35
36.Azeez OI, Oyagbemi AA, Oyeyemi MO, Odetola AA. Ameliorative effects of Cnidoscolus aconitifolius on alloxan toxicity in Wistar rats. Afr Health Sci 2010;10:283-91.  Back to cited text no. 36
37.Sangameswaran B, Jayakar B. Anti-diabetic and spermatogenic activity of Cocculus hirsutus (L) Diels. Afr J Biotechnol 2007;6:1212-6.  Back to cited text no. 37
38.Thakur M, Chauhan NS, Sharma V, Dixit VK, Bhargava S. Effect of Curculigo orchiodes on hyperglycemia-induced oligospermia and sexul dysfunction in male rats. Int J Impot Res 2012;24:31-7.  Back to cited text no. 38
39.Shahreari S, Khaki A, Ahmadi-Ashtiani HR, Rezazadeh S, Hajiaghaei R. Effects of Danae racemosa on testosterone hormone in experimental diabetic rats. J Med Plants 2010;9:114-9.  Back to cited text no. 39
40.Wankeu-Nya M, Florea A, Bâlici S, Watcho P, Matei H, Kamanyi A. Dracaena arborea alleviates ultra-structural spermatogenic alterations in streptozotocin-induced diabetic rats. BMC Complement Altern Med 2013;l13:71. Available from: http://www.biomedcentral.com/1472-6882/13/71 [Last accessed on 2013 Apr 16].  Back to cited text no. 40
41.Ghosh A, Jana K, Ali KM, De D, Chatterjee K, Ghosh D. Corrective role of Eugenia jambolana on testicular impairment in streptozotocin-induced diabetic male albino rat: An approach through genomic and proteomic study. Andrologia 2013. Available from: http://onlinelibrary.wiley.com/doi/10.1111/and. 12081/pdf [Last accessed on 2013 May 09].  Back to cited text no. 41
42.Awang Z, Najib ML, Idzham M, Zarin A. Effect of Ficus deltoidea leaves extracts on sperm quality, LDH-C4 activity and testosterone level in alloxan-induced male diabetic rats. CHUSER 2011. Proceeding of the 2011 IEEE Colloquium on Humanities, Science and Engineering; 2011 Dec 5-6 Penang, Malaysia; 2011. p. 888-91.  Back to cited text no. 42
43.Budin SB, Idris MH, Mohamed J, Osman M. Protective role of Hibiscus sabdariffa calyx extract against streptozotocin induced sperm damage in diabetic rats. Excli J 2012;11:659-69.  Back to cited text no. 43
44.Feng SL, Li SH, Wang Y, Chen CC, Gao B. Effect of ligustrum fruit extract on reproduction in experimental diabetic rats. Asian J Androl 2001;3:71-3.  Back to cited text no. 44
45.Suresh S, Prakash S. Effect of Mucuna pruriens (Linn.) on sexual behavior and sperm parameters in streptozotocin-induced diabetic male rat. J Sex Med 2012;9:3066-78.  Back to cited text no. 45
46.Chatterjee K, Ali KM, De D, Bera TK, Jana K, Maiti S. Diabetes induced testicular dysfunction amelioration by ethyl acetate fraction of hydromethanolic extract of root of Musa paradisiaca L. in streptozotocin-induced diabetic rat. Asian Pac J Trop Dis 2012;Suppl 1:233-41.  Back to cited text no. 46
47.Ghlissi Z, Hamden K, Saoudi M, Sahnoun Z, Mounir Zeghal K, El Fki A, et al. Effects of Nagella sativa seeds on reproductive system of male diabetic rats. Afr J Pharm Pharacol 2012;6:1444-50.  Back to cited text no. 47
48.Asuquo O, Edet A, Mesembe O, Atanghwo J. Ethanolic extracts of Vernonia amygdalina and Ocimum gratissimum enhance testicular improvement in diabetic Wistar rats. Internet J Alternative Med 2010;8:2. Available from: http://archive.ispub.com/journal/ the-internet- journal-of-alternative-medicine/volume-8-number-2/ethanolic- extracts-of-vernonia-amygdalina-and-ocimum-gratissimum- enhance-testicular-improvement-in-diabetic-wistar-rats.html [Last accessed on 2011 Mar 11].  Back to cited text no. 48
49.Ojewale AO, Olaniyan OT, Faduyile FA, Odukanmi OA, Oguntola JA, Dare BJ. Testiculo protective effects of ethanolic roots extract of Pseudocedrela kotschyi on alloxan induced testicular damage in diabetic rats. Br J Med Med Res 2014;4:548-63.  Back to cited text no. 49
50.Khaneshi F, Nasrolahi O, Azizi S, Nejati V. Sesame effects on testicular damage in streptozotocin-induced diabetes rats. Avicenna J Phytomed 2013;3:347-55.  Back to cited text no. 50
51.Abbasi Z, Tabatabaei SR, Mazaheri Y, Barati F, Morovvati H. Effects of sesame oil on the reproductive parameters of diabetes mellitus-induced male rats. World J Mens Health 2013;31:141-9.  Back to cited text no. 51
52.Nah WH, Koh IK, Ahn HS, Kim MJ, Kang HG, Jun JH, et al. Effect of Spirulina maxima on spermatogenesis and steroidogenesis in streptozotocin-induced type I diabetic male rats. Food Chem 2012;134:173-9.  Back to cited text no. 52
53.Ghafari S, Balajadeh BK, Golalipour MJ. Effect of Urtica dioica L. on testicular tissue in STZ-induced diabetic rats. Pak J Biol Sci 2011;14:798-804.  Back to cited text no. 53
54.Irshaid F, Mansi K. Effects of leaf extract of Urtica pilulifera L. on male reproductive system of streptozotocin-diabetic rats. Am J Pharmacol Toxicol 2009;4:22-8.  Back to cited text no. 54
55.Kiasalari Z, Khalili M, Aghaei M. Effect of Withania somnifera on levels of sex hormones in the diabetic male rats. Iran J Reprod Med 2009;7:163-8.  Back to cited text no. 55
56.Nassiri M, Khaki A, Ahmadi-Ashtiani HR, Rezazadeh S, Rastgar H, Gharachurlu S. Effects of ginger on spermatogenesis in streptozotocin-induced diabetic rat. J Med Plants 2009;8:118-24.  Back to cited text no. 56
57.Shalaby MA, Hamowieh AR. Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats. Food Chem Toxicol 2010;48:2920-4.  Back to cited text no. 57
58.Erukainure OL, Okafor OY, Obode OC, Ajayi A, Oluwole OB, Oke OV, et al. Blend of roselle calyx and selected fruit modulates testicular redox status and sperm quality of diabetic rats. J Diabetes Metab 2012;3:1-5.  Back to cited text no. 58
59.Mallick C, Bera TK, Ali KM, Chatterjee K, Ghosh D. Diabetes-induced testicular disorders Vis-à-vis Germ cell apoptosis in albino rat: Ramedial effect of haxane fraction of root of Musa paradisiaca and leaf of Coccinia indica. J Health Sci 2010;56:641-54.  Back to cited text no. 59
60.Mallick C, Mandal S, Barik B, Bhattacharya A, Ghosh D. Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin induced diabetic rat. Biol Pharm Bull 2007;30:84-90.  Back to cited text no. 60
61.Agbai E, Durudola SD, Igbinosun, Mounmbegna PP. Synergistic effect of methanolic extract of Vernonia amygdalina and Ocimum gratissimum on male reproductive hormones in streptozotocin-induced diabetic wistar rats. Int J Biol Sci 2011;3:105-15.  Back to cited text no. 61
62.Joyce OO, Chinwe ND, Nnabufe EJ, Tabot PD, Kwaku JP. Comparative anti-diabetic effects of Ocimium gratissimum, Vernonia amygdalina and insulin on testicular architecture in STZ-induced diabetic rats. Am J Pharm Tech Res 2012;2:279-87.  Back to cited text no. 62


  [Table 1]

This article has been cited by
1 Effect of Kaempferia parviflora on sexual performance in streptozotocin-induced diabetic male rats
T. Lert-Amornpat,C. Maketon,W. Fungfuang
Andrologia. 2017; : e12770
[Pubmed] | [DOI]
2 Quail (Coturnix japonica) egg yolk bioactive components attenuate streptozotocin-induced testicular damage and oxidative stress in diabetic rats
Gideon Oludare Oladipo,Chidinma Martha Nlekerem,Emmanuel Oluwafemi Ibukun,Ayodele Oluseyi Kolawole
European Journal of Nutrition. 2017;
[Pubmed] | [DOI]
3 Protective effects of Lycium barbarum polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice
Guang-Jiang Shi,Jie Zheng,Jing Wu,Hai-Qi Qiao,Qing Chang,Yang Niu,Tao Sun,Yu-Xiang Li,Jian-Qiang Yu
Endocrine Journal. 2017; 64(9): 907
[Pubmed] | [DOI]
4 Gum arabic improves semen quality and oxidative stress capacity in alloxan induced diabetes rats
Jaafar S. Fedail,Abdelkareem A. Ahmed,Hassan H. Musa,Elsadik Ismail,Amal Z. Sifaldin,Taha H. Musa
Asian Pacific Journal of Reproduction. 2016;
[Pubmed] | [DOI]
5 Protective Effects of Scutellarin on Type II Diabetes Mellitus-Induced Testicular Damages Related to Reactive Oxygen Species/Bcl-2/Bax and Reactive Oxygen Species/Microcirculation/Staving Pathway in Diabetic Rat
Lingli Long,Jingnan Wang,Xiaofang Lu,Yuxia Xu,Shuhui Zheng,Canqiao Luo,Yubin Li
Journal of Diabetes Research. 2015; 2015: 1
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Article Tables

 Article Access Statistics
    PDF Downloaded39    
    Comments [Add]    
    Cited by others 5    

Recommend this journal