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Effect of eugenol on lipid profile, oxidative stress, sex hormone, liver injury, ovarian failure, and expression of COX-2 and PPAR-α genes in a rat model of diabetes

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Abstract

Background

Diabetes is among the leading causes of reproductive system failure and infertility in both women and men. Inflammation and oxidative stress have a main role in the development of diabetes. Eugenol or clove oil is a phenolic monoterpenoid with antioxidant and anti-inflammatory properties. Here, the effects of eugenol on diabetes features and ovarian function were investigated.

Methods and results

Streptozotocin-induced diabetes rats were treated with 12 and 24 mg/kg of eugenol for 4 weeks. The biochemical and histological assay was done to evaluate the effects of eugenol on ovary and pancreas function, liver injury, oxidative status, sex hormones, lipid profile, and mRNA levels of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor alpha (PPAR-α) genes. Streptozotocin increased levels of serum glucose, total cholesterol, triglyceride, low-density lipoprotein, aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, pancreas necrosis and inflammation, COX-2 expression, ovarian cystic, and anovulation. It decreased the levels of insulin, high-density lipoprotein, Superoxide dismutase, estradiol, progesterone, testosterone, luteinizing hormone, follicle-stimulating hormone, and PPAR-α expression. Eugenol administration ameliorated diabetes features through the improvement of lipid profile, oxidative status, insulin and glucose levels, sex hormone levels, liver markers, COX-2 and PPAR-α expression, and pancreas histology. It had no effect on ovarian cystic and follicular development.

Conclusions

Therefore, eugenol may be useful for ameliorating some adverse features of diabetes and used as an adjunct treatment or protective agent accompany by other chemicals in diabetes patients.

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Data availability

All datasets generated during the present study are available from the corresponding author on request.

References

  1. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625. https://doi.org/10.2337/diabetes.54.6.1615

    Article  CAS  PubMed  Google Scholar 

  2. Erbas O, Pala HG, Pala EE, Oltulu F, Aktug H, Yavasoglu A, Taskiran D (2014) Ovarian failure in diabetic rat model: nuclear factor-kappaB, oxidative stress, and pentraxin-3. Taiwan J Obstet Gynecol 53:498–503. https://doi.org/10.1016/j.tjog.2013.11.008

    Article  PubMed  Google Scholar 

  3. Pala HG, Pala EE, Artunc Ulkumen B, Aktug H, Yavasoglu A, Korkmaz HA, Erbas O (2014) The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus. Gynecol Obstet Invest 78:94–100. https://doi.org/10.1159/000363239

    Article  CAS  PubMed  Google Scholar 

  4. Erbas O, Pala HG, Pala EE, Artunc Ulkumen B, Akman L, Akman T, Oltulu F, Aktug H, Yavasoglu A (2015) Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study. Gynecol Endocrinol 31:388–391. https://doi.org/10.3109/09513590.2015.1005593

    Article  CAS  PubMed  Google Scholar 

  5. Brand JS, Onland-Moret NC, Eijkemans MJ, Tjonneland A, Roswall N, Overvad K et al (2015) Diabetes and onset of natural menopause: results from the European prospective investigation into cancer and nutrition. Hum Reprod (Oxford, England) 30(6):1491–1498. https://doi.org/10.1093/humrep/dev054

    Article  CAS  Google Scholar 

  6. Hasani-Ranjbar S, Larijani B (2014) Medicinal plants as potential new target drugs in endocrine disorders review article. Iran J Public Health 43:24–34

    Google Scholar 

  7. Shahwan M, Alhumaydhi F, Ashraf GM, Hasan PMZ, Shamsi A (2022) Role of polyphenols in combating Type 2 diabetes and insulin resistance. Int J Biol Macromol 206:567–579. https://doi.org/10.1016/j.ijbiomac.2022.03.004

    Article  CAS  PubMed  Google Scholar 

  8. Km A, Arefeen A, Shamsi A, Alhumaydhi FA, Naseem I (2021) Insight into the in vitro antiglycation and in vivo antidiabetic effects of thiamine: implications of vitamin B1 in controlling diabetes. ACS Omega 6(19):12605–12614. https://doi.org/10.1021/acsomega.1c00631

    Article  CAS  Google Scholar 

  9. Lopes AA, Fonsecau FN, Rocha TM, Freitas LB, Araújo EVO, Wong DVT et al (2018) Eugenol as a promising molecule for the treatment of dermatitis: antioxidant and anti-inflammatory activities and its nanoformulation. Oxid Med Cell Longev 2018:8194849. https://doi.org/10.1155/2018/8194849

    Article  CAS  Google Scholar 

  10. Manikandan P, Vinothini G, Vidya Priyadarsini R, Prathiba D, Nagini S (2011) Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG. Invest New Drugs 29(1):110–117. https://doi.org/10.1007/s10637-009-9345-2

    Article  CAS  PubMed  Google Scholar 

  11. Callejas NA, Casado M, Bosca L, Martín-Sanz P (1999) Requirement of nuclear factor kappa B for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase- 2 in rat trophoblasts. J Cell Sci 112:3147–3155. https://doi.org/10.1242/jcs.112.18.3147

    Article  CAS  PubMed  Google Scholar 

  12. Marnett LJ (2000) Cyclooxygenase mechanisms. Curr Opin Chem Biol 4(5):545–552. https://doi.org/10.1016/s1367-5931(00)00130-7

    Article  CAS  PubMed  Google Scholar 

  13. Poynter ME, Daynes RA (1998) Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappa B signaling, and reduces inflammatory cytokine production in aging. J Biol Chem 273:32833–32841. https://doi.org/10.1074/jbc.273.49.32833

    Article  CAS  PubMed  Google Scholar 

  14. Committee for the update of the guide for the care and use of laboratory animals (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington

    Google Scholar 

  15. Kokabiyan Z, Yaghmaei P, Behnamedin Jameie S, Hajebrahimi Z (2022) Therapeutic effects of eugenol in polycystic ovarian rats induced by estradiol valerate: a histopathological and a biochemical study. International Journal of Fertility and Sterility. https://doi.org/10.22074/IJFS.2021.537724.1176

    Article  PubMed  PubMed Central  Google Scholar 

  16. - Williams CJ, Erickson GF (2003) Morphology and physiology of the ovary. Endotext (Chapter 2). pp 51–58

  17. Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48:2129–2139. https://doi.org/10.1172/JCI106180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Parhofer KG (2015) Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J 39(5):353–362. https://doi.org/10.4093/dmj.2015.39.5.353

    Article  PubMed  PubMed Central  Google Scholar 

  19. JrE W, Scism-Bacon JL, Glass LC (2006) Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract 60(3):308–314. https://doi.org/10.1111/j.1368-5031.2006.00825.x

    Article  CAS  Google Scholar 

  20. Oguntibeju OO (2019) Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol 11(3):45–63

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Gilani SJ, Bin-Jumah MN, Al-Abbasi FA, Nadeem MS, Afzal M, Sayyed N, Kazmi I (2021) Fustin ameliorates hyperglycemia in streptozotocin induced type-2 diabetes via modulating glutathione/superoxide dismutase/catalase expressions, suppress lipid peroxidation and regulates histopathological changes. Saudi J Biol Sci 28(12):6963–6971. https://doi.org/10.1016/j.sjbs.2021.07.070

    Article  CAS  Google Scholar 

  22. Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, Roverato A, Guaraldi G, Lonardo A (2016) Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol 31(5):936–944. https://doi.org/10.1111/jgh.13264

    Article  CAS  PubMed  Google Scholar 

  23. Islam S, Rahman S, Haque T, Sumon AH, Ahmed AM, Ali N (2020) Prevalence of elevated liver enzymes and its association with type 2 diabetes: a cross-sectional study in Bangladeshi adults. Endocrinol Diabetes Metab 3(2):e00116. https://doi.org/10.1002/edm2.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Duckworth WC, Hamel FG, Peavy DE (1988) Hepatic metabolism of insulin. Am J Med 85(5):71–76. https://doi.org/10.1016/0002-9343(88)90399-3

    Article  CAS  PubMed  Google Scholar 

  25. Elkrief L, Rautou PE, Sarin S, Valla D, Paradis V, Moreau R (2016) Diabetes mellitus in patients with cirrhosis: clinical implications and management. Liver Int 36(7):936–948. https://doi.org/10.1111/liv.13115

    Article  CAS  PubMed  Google Scholar 

  26. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (2005) Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54:533–539. https://doi.org/10.1136/gut.2004.052167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Manna P, Das J, Ghosh J, Sil PC (2010) Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF-kappaB, MAPKs, and mitochondria-dependent pathways: prophylactic role of arjunolic acid. Free Radic Biol Med 48:1465–1484. https://doi.org/10.1016/j.freeradbiomed.2010.02.025

    Article  CAS  PubMed  Google Scholar 

  28. Palsamy P, Sivakumar S, Subramanian S (2010) Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin-nicotinamide-induced experimental diabetic rats. Chem Biol Interact 186:200–210. https://doi.org/10.1016/j.cbi.2010.03.028

    Article  CAS  PubMed  Google Scholar 

  29. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50:1844–1850. https://doi.org/10.2337/diabetes.50.8.1844

    Article  CAS  PubMed  Google Scholar 

  30. Pelusi B, Gambineri A, Pasquali R (2004) Type 2 diabetes and the polycystic ovary syndrome. Minerva Ginecol 56(1):41–51

    CAS  PubMed  Google Scholar 

  31. Pala HG, Pala EE, Ulkumen BA, Aktug H, Yavasoglu A, Korkmaz HA, Erbas O (2014) The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus. Gynecol Obstet Invest 78:94–100. https://doi.org/10.1159/000363239

    Article  CAS  PubMed  Google Scholar 

  32. Nayki U, Onk D, Balci G, Nayki C, Onk A, Gunay M (2016) The effects of diabetes mellitus on ovarian injury and reserve: an experimental study. Gynecol Obstet Invest 81:424–429. https://doi.org/10.1159/000442287

    Article  CAS  PubMed  Google Scholar 

  33. Oktay K, Newton H, Mullan J, Gosden RG (1998) Development of human primordial follicles to antral stages in SCID/hpg mice stimulated with follicle stimulating hormone. Hum Reprod 13(5):1133–1138. https://doi.org/10.1093/humrep/13.5.1133

    Article  CAS  PubMed  Google Scholar 

  34. Edson MA, Nagaraja AK, Matzuk MM (2009) The mammalian ovary from genesis to revelation. Endocr Rev 30:624–712. https://doi.org/10.1210/er.2009-0012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Y, Wang Y (2022) Accelerated ovarian aging among type 2 diabetes patients and its association with adverse lipid profile. Front Endocrinol 13:780979. https://doi.org/10.3389/fendo.2022.780979

    Article  Google Scholar 

  36. Wang X, Xian T, Jia X, Zhang L, Liu L, Man F et al (2017) A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients. Medicine 96:e7378. https://doi.org/10.1097/MD.0000000000007378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Natah TM, Abdul- Adheem Wtwt M, Al-Saadi HK, Al-Saadi AH, Farhood HF (2013) Study the levels of adiponectin, FSH, LH and Sex hormones in Type 2 diabetes (NIDDM). J Biol Agric Healthcare 3(2):172–181

    Google Scholar 

  38. Blades RA, Bryant KR, Whitehead SA (1985) Feedback effects of steroids and gonadotrophin control in adult rats with streptozotocin-induced diabetes mellitus. Diabetes Tologia 28:348–354. https://doi.org/10.1007/BF00283142

    Article  CAS  Google Scholar 

  39. Wang Q, Ferreira DLS, Nelson SM, Sattar N, Ala-Korpela M, Lawlor DA (2018) Metabolic characterization of menopause: cross-sectional and longitudinal evidence. BMC Med 16(1):17. https://doi.org/10.1186/s12916-018-1008-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miao C, Chen H, Li Y, Guo Y, Xu F, Chen Q, Zhang Y, Hu M, Chen G (2021) Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats. Diabetol Metab Syndr. https://doi.org/10.1186/s13098-021-00638-3

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hu Y, Chen Y, Ding L, He X, Takahashi Y, Gao Y, Shen W, Cheng R, Chen Q, Qi X, Boulton ME, Ma J (2013) Pathogenic role of diabetes-induced PPAR-α down-regulation in microvascular dysfunction. Proc Natl Acad Sci USA 110(38):15401–15406. https://doi.org/10.1073/pnas.1307211110

    Article  PubMed  PubMed Central  Google Scholar 

  42. Srinivasan S, Sathish G, Jayanthi M, Muthukumaran J, Muruganathan U, Ramachandran V (2014) Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin induced diabetic rats. Mol Cell Biochem 385:159–168. https://doi.org/10.1007/s11010-013-1824-2

    Article  CAS  PubMed  Google Scholar 

  43. Jeong KJ, Kim DY, Quan HY, Jo HK, Kim GW, Chung SH (2014) Effects of eugenol on hepatic glucose production and AMPK signaling pathway in hepatocytes and C57BL/6J mice. Fitoterapia 93:150–162. https://doi.org/10.1016/j.fitote.2013.12.023

    Article  CAS  PubMed  Google Scholar 

  44. Al-Trad B, Alkhateeb H, Alsmadi W, Al- Zoubi M (2019) Eugenol ameliorates insulin resistance, oxidative stress and inflammation in high fat-diet/streptozotocin-induced diabetic rat. Life Sci 216:183–188. https://doi.org/10.1016/j.lfs.2018.11.034

    Article  CAS  PubMed  Google Scholar 

  45. Moghimian M, Aalami S, Abtahi-Evari SH, Soltani M (2018) Effect of Syzygium aromaticum (clove) extract on morphine withdrawal side effect in male reproductive system should be addressed. Physiol Pharmacol 22:109–117

    Google Scholar 

  46. Poli V, Challa C (2019) A comparative study of eugenol and Ocimum sanctum Linn. leaf extract on the antifertility effect in female albino rats. J Chin Med Assoc 82(3):231–234. https://doi.org/10.1097/JCMA.0000000000000034

    Article  PubMed  Google Scholar 

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Acknowledgements

Partial financial support was received from Islamic Azad University, Science and Research Branch, for conducting this study.

Funding

Partial financial support was received from Islamic Azad University, Science and Research Branch, for conducting this study.

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Authors

Contributions

ZK, PY, SBJ, and ZH contributed to conception and designed the experiments. ZK performed experiments and collected data. ZK, PY, SBJ, and ZH discussed the results and strategy; PY, SBJ, and ZH supervised, directed, and managed the study. ZH was the major contributor in writing the manuscript. ZK, PY, SBJ, and ZH final approved of the version to be published.

Corresponding author

Correspondence to Parichehreh Yaghmaei.

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The study was approved by the Animal Care and Use Committee of Islamic Azad University (Ethical permission number: IR.IAU.SRB.REC.1396.51).

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Kokabiyan, Z., Yaghmaei, P., Jameie, S.B. et al. Effect of eugenol on lipid profile, oxidative stress, sex hormone, liver injury, ovarian failure, and expression of COX-2 and PPAR-α genes in a rat model of diabetes. Mol Biol Rep 50, 3669–3679 (2023). https://doi.org/10.1007/s11033-022-08108-3

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