Molecular effects of Moringa leaf extract on insulin resistance and reproductive function in hyperinsulinemic male rats

  • Mona A. MohamedEmail author
  • Mervat A. Ahmed
  • Rasha A. El Sayed
Research article



Many studies have reported that insulin resistance impairs the antioxidant defense system and causes male infertility. Moringa oleifera is a medicinal plant that has been employed for the medicament of many disorders. It controls the levels of glucose and manages male sexual disorders. However, its extracts can reverse insulin resistance-linked metabolic alterations remains unknown. Therefore, the current study investigated the potential of the aqueous leaves extract from Moringa oleifera to reverse insulin resistance and testicular disorders in rats.


Rats were fed either a chow (as a control group) or a high fructose diet (HFD, to persuade a state of insulin resistance), in addition to a group of rats fed HFD and treated with Moringa (300 mg/kg) for 4 weeks.


Moringa reversed hepatic insulin insensitivity and this was linked to up-regulation of genes involved in insulin receptors and glucose uptake in the liver. These results were associated with amended the insulin level in serum and standardization of insulin sensitivity. In addition, it improved the serum testosterone level and the gene expression of the testicular steridogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD).


Taken together, our findings demonstrate that Moringa reversed HFD diet-induced insulin resistance and improved the testicular function.


Insulin resistance Moringa Insulin receptor Glucose transporter StAR 



This study was done in Faculty of Science, Al-Azhar University, Cairo, Egypt. Authors thank the laboratory technical staff in making specimens available for processing. The authors gratefully acknowledge staff of Botany, Zoology and Chemistry Departments, for their organizational support throughout the experimental period.

Funding information

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors declare that there is no conflict of interests in this study.


  1. 1.
    Zagrodzki P, Joniec A, Gawlik M, Gawlik M, Krośniak M, Fołta M, et al. High fructose model of oxidative stress and metabolic disturbances in rats. part I. antioxidant status of rats’ tissues. Bull Vet Inst Pulawy. 2007;51:407–12.Google Scholar
  2. 2.
    Zhang D, Jiao R, Kong L. High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions. Nutrients. 2017;9:335.PubMedCentralCrossRefGoogle Scholar
  3. 3.
    American Diabetes Association. Consensus Development Conference on Insulin Resistance. Diabetes Care. 1997;21:310–4.CrossRefGoogle Scholar
  4. 4.
    Hall JE. Guyton and Hall textbook of medical physiology e-Book. Amsterdam: Elsevier Health Sciences; 2015.Google Scholar
  5. 5.
    Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol. 2019;234:8152–61.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Olatunbosun ST, Schade D. Insulin resistance. eMedicine. Accessed February 26, 2018.Google Scholar
  7. 7.
    Ombelet W, Cooke I, Dyer S, Serour G, Devroey P. Infertility and the provision of infertility medical services in developing countries. Hum Reprod Update. 2008;14:605–21.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Inhorn MC, Patrizio P. Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21:411–26.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Hassan MA, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertil Steril. 2004;81:384–92.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110:1050–8.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Chan O, Chan S, Inouye K, Vranic M, Matthews SG. Molecular regulation of the hypothalamo-pituitary-adrenal axis in streptozotocin-induced diabetes: effects of insulin treatment. Endocrinol. 2001;142:4872–9.CrossRefGoogle Scholar
  12. 12.
    Shi G-J, Zheng J, Wu J, et al. 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 malemice. Endocr J. 2017;64:907–22.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Park K, Gross M, Lee D, Holvoet P, Himes JH, Shikany JM, et al. Oxidative Stress and Insulin Resistance The Coronary Artery Risk Development in Young Adults study. Diabetes Care. 2009;32:1302–7.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Doshi SB, Khullar K, Sharma RK, Agarwal A. Role of reactive nitrogen species in male infertility. Reprod Biol Endocrinol. 2012;10:1–11.CrossRefGoogle Scholar
  15. 15.
    Caceres A, Saravia A, Rizzo S, Zabala L, Leon ED, Nave F. Pharmacology properties of Moringa oleifera. 2: Screening for antispasmodic, antiinflammatory and diuretic activity. J Ethnopharmacol. 1992;36:233–7.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Udupa SL, Udupa AL, Kulkarni DR. Studies on anti-inflammatory and wound healing properties of Moringa oleifera and Aegle marmelos. Fitoterapia. 1994;65:119–23.Google Scholar
  17. 17.
    Pal SK, Mukherjee PK, Saha BP. Studies on the antiulcer activity of Moringa oleifera leaf extract on gastric ulcer models in rats. Phytother Res. 1995;9:463–5.CrossRefGoogle Scholar
  18. 18.
    Prabsattroo T, Wattanathorn J, Iamsa-ard S, Muchimapura S, Thukhammee W. Moringa Oleifera Leaves Extract Attenuates Male Sexual Dysfunction. Am J Neurosci. 2012;3:17–24.Google Scholar
  19. 19.
    Rajasekar P, Kaviarasan S, Anuradha CV. L-carnitine administration prevents oxidative stress in high fructose-fed insulin resistant rats. Diabetol Croat. 2005;34:21–8.Google Scholar
  20. 20.
    Berkovich L, Earon G, Ron I, Rimmon A, Vexler A, Lev-Ari S. Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells. BMC Complement Altern Med. 2013;13:212.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Brieskorn CZ, Klinger H, Polonius W. Triterpenes and sterols in leaves of Salvia trioloba and Pyrus malus. Arch Pharm. 1961;294:389–91.CrossRefGoogle Scholar
  22. 22.
    Geissmann TA. The Chemistry of Flavonoids Compounds. New York: Pergamon Press; 1962.Google Scholar
  23. 23.
    Woo WS, Chi HJ, Yun HS, Hye S. Alkaloid screening of some Saudi Arabian plants. Kor J Pharmacog. 1977;8:109–13.Google Scholar
  24. 24.
    Treare GE, Evans WC. Pharmacognosy. 17th ed. London: Bahiv Tinal; 1985.Google Scholar
  25. 25.
    Kokate CK, Purohit AP, Gokhale SB. Carbohydrate and derived products, drugs containing glycosides, drugs containing tannins, lipids and protein alkaloids. Textbook of Pharmacognosy. 2001.Google Scholar
  26. 26.
    Ahmad B, Naeem AK, Ghufran A, Innamudin I. Pharmacological Investigation of Cassia sophera, Linn. Var. purpura, Roxb. Med J Islam World Academy Sci. 2005;15:105–9.Google Scholar
  27. 27.
    Nikhal SB, Dambe PA, Ghongade DB, Goupale DC. Hydroalcoholic extraction of Mangifera indica (leaves) by Soxhletion. Inter J Pharm Sci. 2010;2:30–2.Google Scholar
  28. 28.
    Jaiswal D, Rai PK, Mehta S, Chatterji S, Shukla S, Rai DK, et al. Role of Moringa oleifera in regulation of diabetes-induced oxidative stress. Asian Pac J Trop Med. 2013;2013:426–32.CrossRefGoogle Scholar
  29. 29.
    Sharp P. Interference in glucose oxidase-peroxidase blood glucose methods. Clin Chem Acta. 1972;40:115–20.CrossRefGoogle Scholar
  30. 30.
    Dhahir FJ, Cook DB, Self CH. Amplified enzyme-linked immunoassay of human pro-insulin in serum. Clin Chem. 1992;38:227–32.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Pickavance LC, Tadayyon M, Widdowson PS, Buckingham RE, Wilding JP. Therapeutic index for rosiglitazone in dietary obese rats. Separation of efficacy and haemodilution. Br J Pharmacol. 1999;128:1570–6.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Rosner W, Auchus RJ, Azzis R. Position statement: utility, limitations, and pitfalls in measuring testosterone: An Endocrine Society Positions Statement. J Clin Endocrinol Metab. 2007;92:404–13.CrossRefGoogle Scholar
  33. 33.
    Clarke JJ, Cummins JT. Pulsatility of reproductive hormones: physiological basis and clinical implications. Baillieres Clin Endocrinol Metab. 1987;1:1–21.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Ohkawa H, Ohishi W, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Nishikimi M, Roa NA. Yogi k. Measurement of superoxide dismutase. Biochem Biophys Res Commun. 1972;46:849–54.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Aebi H. Catalase in vitro. In: Packer L, editor. Methods in Enzymology. Oxygen Radicals in Biological systems. Orlando, FL: Academic Press; 1984. p. 121–6.CrossRefGoogle Scholar
  37. 37.
    Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol. 2014;67:176–86.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Limaye PV, Raghuram N, Sivakami S. Oxidative stress and gene expression of antioxidant enzymes in the renal cortex of streptozotocin-induced diabetic rats. Mol Cell Biochem. 2003;243:147–52.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res. 2007;21:17–25.CrossRefGoogle Scholar
  40. 40.
    Zade VS, Dabhadkar DK, Thakare VG, Pare SR. Effect of Aqueous Extract of Moringa oleifera Seed on Sexual Activity of Male Albino Rats. Biological Forum – An International Journal. 2013;5:129–40.Google Scholar
  41. 41.
    Bailey SA, Zidell RH, Perry RW. Relationships Between Organ Weight and Body/Brain Weight in the Rat: What Is the Best Analytical Endpoint? Toxicol Pathol. 2004;32:448–66.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Kumamoto R, Uto H, Oda K, Ibusuki R, Tanoue S, Arima S, et al. Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat. Eur J Med Res. 2013;18:54.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Schwarz J, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, et al. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endocrinol Metab. 2015;100:2434–42.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Abd El-Wahab HMF, Mohamed MA, El Sayed HH, Bauomy AE. Modulatory effects of rice bran and its oil on lipid metabolism in insulin resistance rats. J Food Biochem. 2017;41:e12318.CrossRefGoogle Scholar
  45. 45.
    Nieto-Vazquez I, Fernández-Veledo S, de Alvaro C, Lorenzo M. Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes. 2008;57:3211–21.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Mahfouz MH, Ghanem HM, Mohamed MA. Modulation of insulin receptor substrate-1 and some inflammatory variables in hyperinsulinemic rats treated with cinnamon extract. Am J Biochem Biotech. 2010;6:11–8.CrossRefGoogle Scholar
  47. 47.
    Hu Y, Hou Z, Yi R, Wang Z, Sun P, Li G, et al. Tartary buckwheat flavonoids ameliorate high fructose-induced insulin resistance and oxidative stress associated with the insulin signaling and Nrf2/HO-1 pathways in mice. Food Funct. 2017;8:2803–16.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    López M, Rios-Silva M, Huerta M, Cárdenas Y, Bricio-Barrios JA, Diaz-Reval MI, et al. Effects of Moringa oleifera leaf powder on metabolic syndrome induced in male Wistar rats: a preliminary study. J Inter Med Res. 2018;46:3327–36.CrossRefGoogle Scholar
  49. 49.
    Munir KM, Chandrasekaran S, Gao F, Quon MJ. Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. Am J Physiol Endocrinol Metab. 2013;305:E679–86.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Nandhini AT, Anuradha CV. Taurine modulates kallikrein activity and glucose metabolism in insulin-resistant rats. Amino Acids. 2002;22:27–38.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Jaiswal D, Rai PK, Kumar A, Mehta S, Watal G. Effect of Moringa oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol. 2009;123:392–6.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Kumari DJ. Hypoglycemic effect of Moringa oleifera and Azadirachta indica in type-2 diabetes. Bioscan. 2010;5:211–4.Google Scholar
  53. 53.
    Yassa HD, Tohamy AF. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced diabetes mellitus in adult rats. Acta Histochem. 2014;116:844–54.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Tende JA, Ezekiel I, Dikko AAU, Goji ADT. Effect of Ethanolic Leaves Extract of Moringa oleifera on Blood Glucose Levels of Streptozocin-Induced Diabetics and Normoglycemic Wistar Rats. Br J Pharmacol Toxicol. 2011;2:1–4.Google Scholar
  55. 55.
    Abdel-Kawi SH, Hassanin KM, Hashem KS. The effect of high dietary fructose on the kidney of adult albino rats and the role of curcumin supplementation: A biochemical and histological study. Beni-Suef Univ J Basic App Sci. 2016;5:52–60.CrossRefGoogle Scholar
  56. 56.
    Akunna GG, Ogunmodede OS, Saalu CL, Ogunlade B, Bello AJ, Salawu EO. Ameliorative Effect of Moringa oleifera (drumstick) Leaf Extracts on Chromium-Induced Testicular Toxicity in Rat Testes. World J Life Sci and Med Res. 2012;2:20.Google Scholar
  57. 57.
    Diemer T, Allen JA, Hales KH, Hales DB. Reactive oxygen disrupts mitochondria in MA-10 tumor leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology. 2003;144:2882–91.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Christenson LK, Strauss I, Jerome F. Steroidogenic acute regulatory protein; an update on its regulation and mechanism of action. Arch Med Res. 2001;32:576–86.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Stocco DM. StAR protein and the regulation of steroid hormone biosynthesis. Annu Rev Physiol. 2001;63:193–213.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Rasmussen MK, Ekstrand B, Zamaratskaia G. Regulation of 3β-Hydroxysteroid dehydrogenase/ Δ5-Δ4 isomerase: A Review. Int J Mol Sci. 2013;14:17926–42.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Allen C, McLachlan R. Testosterone deficiency in men: diagnosis and management. Aust Family Phys. 2003;32:422–9.Google Scholar
  62. 62.
    Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol. 2013;36:353–68.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Kim ST, Moley KH. Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. Reproduction. 2008;136:313–22.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Priyadarshani N, Varma MC. Effect of Moringa oleifera leaf powder on sperm count, histology of testis and epididymis of hyperglycaemic mice Mus musculus. Am Inter J Res For Appl Nat Sci. 2014;7:7–13.Google Scholar
  65. 65.
    Pasquali R, Casimirri F, Cantobelli S, Melchionda N, Morselli Labate AM, Fabbri R, et al. Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism. 1991;40:101–4.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Shukla VN, Khanuja SP. Chemical, Pharmacological and botanical studies on Pedalium murex. J Med Aromatic Plant Sci. 2004;26:64–96.Google Scholar
  67. 67.
    Padashetty SA, Mishra SH. Aphrodisiac studies of Tricholepis glaberrima with supportive action from antioxidant enzyme. Pharm Biol. 2007;45:580–6.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mona A. Mohamed
    • 1
    Email author
  • Mervat A. Ahmed
    • 2
    • 3
  • Rasha A. El Sayed
    • 2
  1. 1.Biochemistry Division, Chemistry Department, Faculty of ScienceAl-Azhar University (Girls Branch)CairoEgypt
  2. 2.Zoology Department, Faculty of ScienceAl-Azhar University (Girls Branch)CairoEgypt
  3. 3.Biology Department, Faculty of ScienceBisha UniversityBishaSaudi Arabia

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