Effects of Eryngium Caucasicum Extract on Testosterone, Inflammation and Oxidative Status of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Rats

  • Masood Afshari Department of Nutrition, Jundishapour University of Medical Sciences, Ahvaz, Iran.
  • Ali Reza Malayeri Medical Plant Research Center, Jundishapour University of Medical Sciences. Ahvaz, Iran.
  • Majid Mohammadshahi Department of Nutrition, Hyperlipidemia Research Center, Jundishapour University of Medical Sciences. Ahvaz, Iran.


Objective: Regarding the unfavorable side effects of anti-diabetic drugs including peripheral edema, gastrointestinal discomfort and hypoglycemia, using medicinal plants due to their useful contents such as flavonoids, alkaloids, glycopeptides, terpenoides, phenolic compounds and other constituents with antioxidant and anti-inflammatory effects, is encouraged in treatment of diabetes mellitus. Thus, the hypothesis was that Eryngium Caucasicum extract will decrease inflammation and oxidative stress in nicotinamide-streptozotocin induced type 2 diabetes mellitus model in Wistar rats.
Methods: In this study, sixty adult male Wistar rats (150 – 250 g) were randomly allocated into six groups (n=10) including: 1: healthy control, 2: diabetic control, 3: diabetic rats which received Sitagliptine, 4, 5 and 6: diabetic rats which received 100, 200 and 300 mg/kg of E. Caucasicum extract oral gavages for 30 days. Eventually, total antioxidant capacity, vitamin B12, malondyaldehyde, interleukin-6, high sensitive C - reactive protein and testosterone serum levels were measured.
Results: Administration of E. Caucasicum in type 2 diabetes mellitus animal model did not change serum vitamin B12 and animal weight compared with control groups. Total antioxidant capacity and malondyaldehyde improved in all doses of E. Caucasicum; in the highest doses, the total antioxidant capacity was higher than sitagliptine group. Interleukin-6 and high sensitive C-reactive protein both decreased in all doses of E. Caucasicum. Administration of E. Caucasicum extract improved testosterone serum level only in highest dose of E. Caucasicum extract. Since the highest dose showed the highest antioxidant and anti-inflammatory effects; dose-responses of antioxidant and anti-inflammatory effects are suggested.
Conclusions: In conclusion, we showed that administration of E. Caucasicum in T2DM animal model has antioxidant and anti-inflammatory effects. However, in future studies other dose-escalating intervention must be performed. Also toxicity in diabetes must be elucidated in future studies.
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1. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nature Reviews Disease Primers. 2015;1:15019. doi: 10.1038/nrdp.2015.19.
2. Control CfD, Prevention. National diabetes statistics report, 2017. Atlanta, GA: Centers for Disease Control and Prevention. 2017.
3. Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, et al. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes research and clinical practice. 2010;87(3):293-301.
4. Chan GC, Tang SC. Diabetic nephropathy: landmark clinical trials and tribulations. Nephrology Dialysis Transplantation. 2015;31(3):359-68.
5. Akash MS, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. Journal of cellular biochemistry. 2013;114(3):525-31. Epub 2012/09/20. doi: 10.1002/jcb.24402. PubMed PMID: 22991242.
6. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Jama. 2001;286(3):327-34.
7. Donath MY, Dalmas É, Sauter NS, Böni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell metabolism. 2013;17(6):860-72.
8. Kitamura T. The role of FOXO1 in β-cell failure and type 2 diabetes mellitus. Nature Reviews Endocrinology. 2013;9(10):615.
9. Ghorbani A. Best herbs for managing diabetes: A review of clinical studies. Brazilian Journal of Pharmaceutical Sciences. 2013;49(3):413-22.
10. Rao MU, Sreenivasulu M, Chengaiah B, Reddy KJ, Chetty CM. Herbal medicines for diabetes mellitus: a review. Int J PharmTech Res. 2010;2(3):1883-92.
11. Ji HF, Li XJ, Zhang HY. Natural products and drug discovery: can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO reports. 2009;10(3):194-200.
12. Calvino CI, Martínez SG, Downie SR. The evolutionary history of Eryngium (Apiaceae, Saniculoideae): Rapid radiations, long distance dispersals, and hybridizations. Molecular phylogenetics and evolution. 2008;46(3):1129-50.
13. Nabavi S, Nabavi S, Alinezhad H, Zare M, Azimi R. Biological activities of flavonoid-rich fraction of Eryngium caucasicum Trautv. European review for medical and pharmacological sciences. 2012;16:81-7.
14. WORZ A. On the distribution and relationships of the South-West Asian species of Eryngium L.(Apiaceae-Saniculoideae). Turkish Journal of Botany. 2004;28(1-2):85-92.
15. Trautv P. Plants for a future, edible, medicinal and useful plants for a healthier world, Eryngium caucasicum. 2004.
16. Riekandeh SM, Mazandarani M, Ebrahimzadeh MA, Zargari M. Antioxidant activities of Eryngium caucasicum inflorescence. European Review for Medical and Pharmacological Sciences. 2016;20(5):946-9. PubMed PMID: WOS:000373350100028.
17. Küpeli E, Kartal M, Aslan S, Yesilada E. Comparative evaluation of the anti-inflammatory and antinociceptive activity of Turkish Eryngium species. Journal of ethnopharmacology. 2006;107(1):32-7.
18. Wang P, Su Z, Yuan W, Deng G, Li S. Phytochemical constituents and pharmacological activities of Eryngium L.(Apiaceae). 2012.
19. Ben Lajnef H, Ferioli F, Pasini F, Politowicz J, Khaldi A, Filippo D'Antuono L, et al. Chemical composition and antioxidant activity of the volatile fraction extracted from air‐dried fruits of Tunisian Eryngium maritimum L. ecotypes. Journal of the Science of Food and Agriculture. 2018;98(2):635-43.
20. Marčetić M, Petrović S, Milenković M, Niketić M. Composition, antimicrobial and antioxidant activity of the extracts of Eryngium palmatum Pančić and Vis.(Apiaceae). Open Life Sciences. 2014;9(2):149-55.
21. Erdem SA, Nabavi SF, Orhan IE, Daglia M, Izadi M, Nabavi SM. Blessings in disguise: a review of phytochemical composition and antimicrobial activity of plants belonging to the genus Eryngium. DARU Journal of Pharmaceutical Sciences. 2015;23(1):53.
22. Merghache D, Boucherit-Otmani Z, Merghache S, Chikhi I, Selles C, Boucherit K. Chemical composition, antibacterial, antifungal and antioxidant activities of Algerian Eryngium tricuspidatum L. essential oil. Natural product research. 2014;28(11):795-807. Epub 2014/02/25. doi: 10.1080/14786419.2014.883392. PubMed PMID: 24559136.
23. Nabavi SM, Nabavi SF, Alinezhad H, Zare M, Azimi R. Biological activities of flavonoid-rich fraction of Eryngium caucasicum Trautv. Eur Rev Med Pharmacol Sci. 2012;16 Suppl 3:81-7. Epub 2012/09/11. PubMed PMID: 22957421.
24. Khalili M, Dehdar T, Hamedi F, Ebrahimzadeh MA, Karami M. Antihypoxic activities of Eryngium caucasicum and Urtica dioica. European Review for Medical and Pharmacological Sciences. 2015;19(17):3282-5. PubMed PMID: WOS:000361837100028.
25. Ebrahimzadeh M, Nabavi S, Nabavi S, Pourmorad F. Nitric oxide radical scavenging potential of some Elburz medicinal plants. African journal of Biotechnology. 2010;9(32):5212-7.
26. Rjeibi I, Saad AB, Ncib S, Souid S. Phenolic composition and antioxidant properties of Eryngium maritimum (sea holly). Journal of Coastal Life Medicine. 2017;5(5):212-5.
27. Dawilai S, Muangnoi C, Praengamthanachoti P, Tuntipopipat S. Anti-inflammatory activity of bioaccessible fraction from Eryngium foetidum leaves. BioMed research international. 2013;2013.
28. Jaghabir M. Hypoglycemic effects ofEryngium creticum. Archives of Pharmacal Research. 1991;14(4):295-7.
29. Afrin R, Arumugam S, Soetikno V, Thandavarayan R, Pitchaimani V, Karuppagounder V, et al. Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats. Free radical research. 2015;49(3):279-89.
30. Akinlade K, Agbebaku S, Rahamon S, Balogun W. Vitamin B 12 levels in patients with type 2 diabetes mellitus on metformin. Annals of Ibadan postgraduate medicine. 2015;13(2):79-83.
31. Leporatti ML, Ivancheva S. Preliminary comparative analysis of medicinal plants used in the traditional medicine of Bulgaria and Italy. Journal of ethnopharmacology. 2003;87(2-3):123-42.
32. Ali-Shtayeh M, Yaghmour RM-R, Faidi Y, Salem K, Al-Nuri M. Antimicrobial activity of 20 plants used in folkloric medicine in the Palestinian area. Journal of Ethnopharmacology. 1998;60(3):265-71.
33. Gruenwald J, Brendler T, Jaenicke C. PDR for herbal medicines: Thomson, Reuters; 2007.
34. Benoit P, Fong H, Svoboda G, Farmsworth N. Biological and phytochemical evaluation of plants. XIV. Antiinflammatory evaluation of 163 species of plants. Lloydia. 1976;39(2-3):160-71.
35. Lisciani R, Fattorusso E, Surano V, Cozzolino S, Giannattasio M, Sorrentino L. Anti-inflammatory activity of Eryngium maritimum L. rhizome extracts in intact rats. Journal of ethnopharmacology. 1984;12(3):263-70.
36. Yesilada E, Tanaka S, Tabata M, Sezik E. The antiinflammatory activity of the fractions from Eryngium billardieri in mice. Phytotherapy Research. 1989;3(1):38-40.
37. Garcia M, Saenz M, Gomez M, Fernandez M. Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 1999;13(1):78-80.
38. Mekhora C, Muangnoi C, Chingsuwanrote P, Dawilai S, Svasti S, Chasri K, et al. Eryngium foetidum suppresses inflammatory mediators produced by macrophages. Asian Pacific journal of cancer prevention : APJCP. 2012;13(2):653-64. Epub 2012/04/25. PubMed PMID: 22524841.
39. Nabavi S, Ebrahimzadeh M, Nabavi S, Bahramian F. In vitro antioxidant activity of Phytolacca americana berries. Pharmacologyonline. 2009;1(2009):81-8.
40. Saenz M, Fernandez M, Garcia M. Antiinflammatory and analgesic properties from leaves of Eryngium foetidum L.(Apiaceae). Phytotherapy Research: An International Journal Devoted to Medical and Scientific Research on Plants and Plant Products. 1997;11(5):380-3.
41. Khaneshi F, Nasrolahi O, Azizi S, Nejati V. Sesame effects on testicular damage in streptozotocin-induced diabetes rats. Avicenna journal of phytomedicine. 2013;3(4):347-55. Epub 2014/07/23. PubMed PMID: 25050292; PubMed Central PMCID: PMCPMC4075729.
42. Lin T, Haskell J, Vinson N, Terracio L. Characterization of insulin and insulin-like growth factor I receptors of purified Leydig cells and their role in steroidogenesis in primary culture: a comparative study. Endocrinology. 1986;119(4):1641-7. Epub 1986/10/01. doi: 10.1210/endo-119-4-1641. PubMed PMID: 2944738.
43. Kalyani RR, Dobs AS. Androgen deficiency, diabetes, and the metabolic syndrome in men. Current opinion in endocrinology, diabetes, and obesity. 2007;14(3):226-34. Epub 2007/10/18. doi: 10.1097/MED.0b013e32814db856. PubMed PMID: 17940444.
44. Zhao YT, Qi YW, Hu CY, Chen SH, Liu Y. Advanced glycation end products inhibit testosterone secretion by rat Leydig cells by inducing oxidative stress and endoplasmic reticulum stress. International journal of molecular medicine. 2016;38(2):659-65. Epub 2016/06/18. doi: 10.3892/ijmm.2016.2645. PubMed PMID: 27315604.
45. Rojas D, Pandey A. Natural Compounds to Counteract Testosterone Depletion in Aging. J Steroids Horm Sci. 2014;5:e112.
How to Cite
AFSHARI, Masood; MALAYERI, Ali Reza; MOHAMMADSHAHI, Majid. Effects of Eryngium Caucasicum Extract on Testosterone, Inflammation and Oxidative Status of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Rats. Journal of Contemporary Medical Sciences, [S.l.], v. 5, n. 2, apr. 2019. ISSN 2413-0516. Available at: <http://www.jocms.org/index.php/jcms/article/view/568>. Date accessed: 23 jan. 2021.