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The effect of Ferula elaeochytris root extract on erectile dysfunction in streptozotocin-induced diabetic rat

International Journal of Impotence Research (2019) | Download Citation

Abstract

Erectile dysfunction (ED) is an important complication of diabetes. The aim of our study was to determine whether Ferula elaeochytris (FE) root extract could affect ED in streptozotocin (STZ)-induced diabetic rats. Seventy-five adult male Wistar albino rats were equally divided into five groups; control (C), FE (40 mg/kg-d), STZ-induced diabetes (60 mg/kg) (DM), diabetes + F. elaeochytris (DM + FE), and ethanol (EtOH). After 8 weeks, in vitro and in vivo parameters (intracavernosal pressure [ICP]), testicle and body weight, serum glucose levels, and histopathology were assessed. In the STZ-induced diabetic group, acetylcholine-induced endothelium-dependent relaxation responses, and electrical field stimulation-induced neurogenic and nitrergic relaxation responses were decreased significantly, while FE administration to diabetic rats reversed the decreased nitrergic and neurogenic responses. In the diabetic group, ICP/MAP (0.1375 ± 0.02 cm/H2O), spermatogenesis in testicles (53.73 ± 0.81), and testicle weights (257.8 ± 20.63) were decreased significantly; however, FE administration to diabetic rats restored the decreased values (0.350 ± 0.019 cm/H2O, 75.07 ± 0.35, and 416 ± 24.11, respectively). In the DM group, blood glucose levels were increased (411.7 ± 18.30) compared to the C group. However, FE administration to diabetic rats reduced glucose levels (230.6 ± 25.60 mg/dL) compared to the DM group. In conclusion, FE recovered neurogenic and endothelial dysfunction and decreased glucose levels in diabetic rats.

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References

  1. 1.

    Martinez AC, Prieto D, Raposo R, Delgado JA, Resel L, Garcia-Sacristan A, et al. Endothelium-independent relaxation induced by histamine in human dorsal penile artery. Clin Exp Pharm Physiol. 2000;27:500–7.

  2. 2.

    Hakim LS, Goldstein I. Diabetic sexual dysfunction. Endocrinol Metab Clin North Am. 1996;25:379–400.

  3. 3.

    Kouidrat Y, Pizzol D, Cosco T, Thompson T, Carnaghi M, Bertoldo A, et al. High prevalence of erectile dysfunction in diabetes: a systematic review and meta-analysis of 145 studies. Diabet Med. 2017;34:1185–92.

  4. 4.

    Maggi F, Cecchini C, Cresci A, Coman MM, Trillini B, Sagratini G, et al. Chemical composition and antimicrobial activity of the essential oil from Ferula glauca L. (F. communis L. subsp. glauca) growing in Marche (central Italy). Fitoterapia . 2009;80:68–72.

  5. 5.

    Appendino G. The toxins of Ferula communis L, in: L. Verrotta (ed.), Virtual activity, Real Pharmacology, 1997;1:1–15.

  6. 6.

    Akaberi M, Iranshahy M, Iranshahi M. Review of the traditional uses, phytochemistry, pharmacology and toxicology of giant fennel (Ferula communis L. subsp. communis). Iran J Basic Med Sci. 2014;18:1052–62.

  7. 7.

    Homady MZ, Khleifat KM, Tarawneh KK, Al-Raheil IA. Reproductive toxicity and fertility effect of Ferula hermonis extracts in mice. Theriogenology. 2002;57:2247–56.

  8. 8.

    Kavoosi G, Rowshan V. Chemical composition, antioxidant and antimicrobial activities of essential oil obtained from Ferula assa-foetidaoleo-gum-resin: effect of collection time. Food Chem. 2013;138:2180–7.

  9. 9.

    Kavoosi G, Tafsiry A, Ebdam AA, Rowshan V. Evaluation of antioxidant and antimicrobial activities of essential oils from Carum copticum seed and Ferula assafoetida latex. J Food Sci. 2013;78:356–61.

  10. 10.

    Geroushi A, Auzi AA, Elhwuegi AS, Elzawam F, Elsherif A, Nahar L, et al. Antiinflammatory sesquiterpenes from the root oil of Ferula hermonis. Phytother Res. 2011;25:774–7.

  11. 11.

    Macho A, Blanco-Molina M, Spagliardi P, Appendino G, Bremner P, Heinrich M, et al. Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line. Biochem Pharm. 2004;68:875–83.

  12. 12.

    Abu-Zaiton AS. Anti-diabetic activity of Ferula assafoetida extract in normal and alloxan-induced diabetic rats. Pak J Biol Sci. 2010;13:97–100.

  13. 13.

    Kose EO, Akta Ö, Deniz IG, Sarikürkçü C. Chemical composition, antimicrobial and antioxidant activity of essential oil of endemic Ferula lycia Boiss. J Med Plant Res. 2010;4:1698–703.

  14. 14.

    Singh R. In vitro evaluation of aqueous and alcoholic extracts of spices for antifungal properties. Indian J Anim Sci. 2007;77:675–7.

  15. 15.

    Sadraei H, Asghari GR, Hajhashemi V, Kolagar A, Ebrahimi M. Spasmolytic activity of essential oil and various extracts of Ferula gummosa Boiss. on ileum contractions. Phytomedicine. 2001;8:370–6.

  16. 16.

    Agrawal AK, Rao CV, Sairam K, Joshi VK, Goel PK. Effect of Piper longum Linn, Zingiber officinalis Linn and Ferula species on gastric ulceration and secretion in rats. Indian J Exp Biol. 2000;38:994–8.

  17. 17.

    Kassis E, Fulder S, Khalil K, Hadieh B, Nahhas F, Saad B, et al. Efficacy and safety assessments of Ferula assa-foetida L., traditionally used in Greco-Arab herbal medicine for enhancing male fertility, libido and erectile function. Open Compl Med J. 2009;1:02–109.

  18. 18.

    Khleifat K, Homady MH, Tarawneh KA, Shakhanbeh J. Effect of ferula hormonis extract on social aggression, fertility and some physiological parameters in prepubertal male mice. Endocr J. 2001;48:473–82.

  19. 19.

    Ozturk B, Gur S, Coskun M, Kosan M, Erdurak CS, Hafez G, et al. New relaxant on human corpus cavernosum: Ferulago syriaca root extract. Afr J Pharm Pharmacol. 2012;6:2652–6.

  20. 20.

    Liu H, Lin S, Lv Q, Yang Q, Wu G, Hu J, et al. Taurine recovers testicular steroidogenesis and spermatogenesis in streptozotocin-induced diabetic rats. Adv Exp Med Biol. 2017;975:801–11.

  21. 21.

    Bimakr M, Rahman RA, Taip FS, Ganjloo A, Salleh LM, Selamet J, et al. Comparison of different extraction methods for the extraction of major bioactive flavonoid compounds from spearmint (Mentha spicata L.) leaves. Food Bioprod Process. 2011;89:67–72.

  22. 22.

    Bai Y, An R. Resveratrol and sildenafil synergistically improve diabetes-associated erectile dysfunction in streptozotocin-induced diabetic rats. Life Sci. 2015;135:43–48.

  23. 23.

    Göçmen C, Seçilmiş MA, Kumcu E, Ertuğ FP, Önder S, Dikmen A, et al. “Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse”. Eur J Pharmacol. 2000;398:93–98.

  24. 24.

    Leblond CR, Clermont Y. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann NY Acad Sci. 1952;55:548–73.

  25. 25.

    Johnsen SG. Testicular biopsy score count—a method for registration of spermatogenesis in human testes: normal value and results of 355 hypogonadal males. Hormones. 1970;1:2–25.

  26. 26.

    Keegan A, Cotter MA, Cameron NE. Effects of diabetes and treatment with the antioxidant a-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats. Diabetologia. 1999;42:343–50.

  27. 27.

    Keegan A, Cotter MA, Cameron NE. Corpus cavernosum dysfunction in diabetic rats: effects of combined alpha-lipoic acid and gamma-linolenic acid treatment. Diabetes Metab Res Rev. 2001;17:380–6.

  28. 28.

    Bivalacqua T, Usta M, Champion H, Leungwattanakij S, Dabisch P, McNamara D, et al. Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res. 2004;16:21–29.

  29. 29.

    Zhang XH, Filippi S, Morelli A, Vignozzi L, Luconi M, Donati S, et al. Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med. 2006;3:253–64.

  30. 30.

    Raafat K, El-Lakany A. Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L. and their potential active isolates in a diabetic mouse model of neuropathic pain. BMC Complement Alter Med. 2015;15:257.

  31. 31.

    Türkez H, Aydın E. In vitro assessment of cytogenetic and oxidative effects of α-pinene. Toxicol Ind Health. 2013;32:168–76.

  32. 32.

    Asokkumar S, Naveenkumar C, Raghunandhakumar S, Kamaraj S, Anandakumar P, Jagan S, et al. Antiproliferative and antioxidant potential of beta-ionone against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice. Mol Cell Biochem. 2012;363:335–45.

  33. 33.

    Azadzoi KM, Saenz de Tejada I. Diabetes mellitus impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol. 1992;148:1587–91.

  34. 34.

    Kahler W, Kuklinski B, Ruhlmann C, Plotz C.Diabetes Mellitus; a free radical associated disease. Results of adjuvant antioxidant supplementation.lnn Med. 1993;48:223–32.

  35. 35.

    Ahn GJ, Sohn YS, Kang KK, Ahn BO, Kwon JW, Kang SK, et al. The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats. Int J Impot Res. 2005;17:134–41.

  36. 36.

    Thakur M, Chauhan NS, Sharma V, Dixit VK, Bhargava S. Effect of Curculigo orchioides on hyperglycemia-induced oligospermia and sexual dysfunction in male rats. Int J Impot Res. 2012;24:31–37.

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Acknowledgements

We would like to thank Assoc. Prof. Dr. Atilla Yoldas and Prof. Dr. Sena Sezen to contribute the article. We also thank Scientific Research Projects of Cukurova University (TDK-2015-1996) and also The Scientific and Technological Research Council of Turkey (TUBITAK) to support this study as a scholar of 2211-C-Domestic-Doctoral-Scholarship-Program for Priority-Areas (2014-1).

Author information

Affiliations

  1. Faculty of Medicine, Department of Pharmacology, University of Kahramanmaras Sutcu Imam, Kahramanmaras, Turkey

    • Nadire Eser
  2. Faculty of Pharmacy, Department of Pharmacology, University of Cukurova, Adana, 01330, Turkey

    • Hacer Sinem Buyuknacar
  3. Faculty of Medicine, Department of Pharmacology, University of Cukurova, Adana, 01330, Turkey

    • Ozge Ozturk Cimentepe
    •  & Cemil Gocmen
  4. Faculty of Fisheries, Department of Seafood Processing Technology, University of Cukurova, Adana, 01330, Turkey

    • Yilmaz Ucar
  5. Faculty of Medicine, Department of Pathology, University of Cukurova, Adana, 01330, Turkey

    • Seyda Erdogan
  6. Department of Urology, University of Yamanashi Graduate School of Medicine, Chuo, Yamanashi, 409-3898, Japan

    • Mitsuharu Yoshiyama

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The authors declare that they have no conflict of interest.

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Correspondence to Nadire Eser.

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DOI

https://doi.org/10.1038/s41443-019-0137-8