A Comparison between Antioxidant Effects of Korean Red Ginseng Extract (KRGE)-Loaded Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles and Korean Red Ginseng Extract (KRGE) in the Treatment of Testosterone-Induced Polycystic Ovarian Syndrome

Document Type : Original Article (s)

Authors

1 PhD Student, Department of Biology, School of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran

2 Assistant Professor, Department of Biology, School of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran

3 Associate Professor, Department of Biology, School of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran

Abstract

Background: This study aimed to evaluate and compare the effects of Korean red ginseng extract (KRGE) and KRGE-loaded poly(lactic-co-glycolic acid) nanoparticles (KRGE-loaded PLGA NPs) on testosterone-induced polycystic ovarian syndrome (PCOS) mice.Methods: Female Naval Medical Research Institute (NMRI) post-pubertal mice were divided into control (n = 10), sham (n = 10), and PCOS (n = 60) groups. PCOS was induced in sham and PCOS groups by subcutaneous injection of testosterone enanthate 1 mg/100mg/day in the back of the mice neck for 4 weeks; then, the PCOS group was intraperitoneally treated with different concentrations of KRGE and KRGE-loaded PLGA NPs for the consecutive 15 days. The ovarian tissues were surgically removed for determinations of malondialdehyde (MDA), reactive oxygen species, glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), and qualitative real-time polymerase chain reaction (qRT-PCR) analysis to detect glutathione reductase (GR) and nuclear factor erythroid 2 (NRF-2) genes.Findings: Both KRGE and KRGE-loaded PLGA NPs were beneficial to decrease MDA, and oxidative agents as well as increase the level of GSH, TAC, and GST in PCOS mice. According to qRT-PCR analysis, the expressions of NRF-2 and GR genes were elevated in the treated mice. However, statistical analysis revealed that KRGE-loaded PLGA NPs were more effective than KRGE.Conclusion: Our results are consistent with the beneficial effect of KRGE on the treatment of PCOS. Nonetheless, KRGE coated with PLGA NPs were suggested more effective according to our findings.

Keywords


  1. Behboodi Moghadam Z, Fereidooni B, Saffari M, Montazeri A. Polycystic ovary syndrome and its impact on Iranian women's quality of life: A population-based study. BMC Womens Health 2018; 18(1): 164.
  2. Moradi N, Bidgoli SA, Chaichian S. Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome. Obstet Gynecol Sci 2021; 64(3): 274-83.
  3. Bani MM, Majdi SA. Polycystic ovary syndrome (PCOS), diagnostic criteria, and AMH. Asian Pac J Cancer Prev 2017; 18(1): 17-21.
  4. Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature 2012; 490(7419): 187-91.
  5. Paris VR, Bertoldo MJ. The mechanism of androgen actions in PCOS etiology. Med Sci (Basel) 2019; 7(9): 89.
  6. Azziz R. Androgen excess is the key element in polycystic ovary syndrome. Fertil Steril 2003; 80(2): 252-4.
  7. Keefe CC, Goldman MM, Zhang K, Clarke N, Reitz RE, Welt CK. Simultaneous measurement of thirteen steroid hormones in women with polycystic ovary syndrome and control women using liquid chromatography-tandem mass spectrometry. PLoS One 2014; 9(4): e93805.
  8. Palomba S, Falbo A, Chiossi G, Muscogiuri G, Fornaciari E, Orio F, et al. Lipid profile in nonobese pregnant women with polycystic ovary syndrome: A prospective controlled clinical study. Steroids 2014; 88: 36-43.
  9. Faure M, Bertoldo MJ, Khoueiry R, Bongrani A, Brion F, Giulivi C, et al. Metformin in reproductive biology. Front Endocrinol (Lausanne) 2018; 9: 675.
  10. Kar S, Sanchita S. Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial. J Hum Reprod Sci 2015; 8(4): 197-201.
  11. Arentz S, Smith CA, Abbott J, Bensoussan A. Nutritional supplements and herbal medicines for women with polycystic ovary syndrome; a systematic review and meta-analysis. BMC Complement Altern Med 2017; 17(1): 500.
  12. Kwon CY, Cho IH, Park KS. Therapeutic effects and mechanisms of herbal medicines for treating polycystic ovary syndrome: A review. Front Pharmacol 2020; 11: 1192.
  13. Choi JH, Jang M, Kim EJ, Lee MJ, Park KS, Kim SH, et al. Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities. J Ginseng Res 2020; 44(6): 790-8.
  14. Jung JH, Park HT, Kim T, Jeong MJ, Lim SC, Nah SY, et al. Therapeutic effect of Korean red ginseng extract on infertility caused by polycystic ovaries. J Ginseng Res 2011; 35(2): 250-5.
  15. Chen S, Wang Z, Huang Y, O'Barr SA, Wong RA, Yeung S, et al. Ginseng and anticancer drug combination to improve cancer chemotherapy: A critical review. Evid Based Complement Alternat Med 2014; 2014: 168940.
  16. Ganesan P, Ko HM, Kim IS, Choi DK. Recent trends of nano bioactive compounds from ginseng for its possible preventive role in chronic disease models. RSC Adv 2015; 5(119): 98634-42.
  17. Pandey A, Jain DS. Poly lactic-co-glycolic acid (PLGA) copolymer and its pharmaceutical application. In: Thakur VK, Thakur MK, editors. Handbook of polymers for pharmaceutical technologies. Hoboken, NJ: Wiley; 2015. p. 151-72.
  18. Rezvantalab S, Drude NI, Moraveji MK, Guvener N, Koons EK, Shi Y, et al. PLGA-based nanoparticles in cancer treatment. Front Pharmacol 2018; 9: 1260.
  19. Sadoghi SD, Rahbariyan R. Investigation the effect of glycyrrhizic acid on ovarian follicle in polycystic ovarian syndrome mice model. J Ilam Univ Med Sci 2017; 24(6): 138-48. [In Persian].
  20. Malini NA, Roy GK. Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - Clinical based case control study. Gen Comp Endocrinol 2018; 260: 51-7.
  21. Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC Complement Altern Med 2014; 14: 511.
  22. Ashraf S, Nabi M, Rasool SuA, Rashid F, Amin S. Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: A review. Egypt J Med Hum Genet 2019; 20(1): 25.
  23. Deepika ML, Nalini S, Maruthi G, Ramchander V, Ranjith K, Latha KP, et al. Analysis of oxidative stress status through MN test and serum MDA levels in PCOS women. Pak J Biol Sci 2014; 17(4): 574-7.
  24. Palacio JR, Iborra A, Ulcova-Gallova Z, Badia R, Martinez P. The presence of antibodies to oxidative modified proteins in serum from polycystic ovary syndrome patients. Clin Exp Immunol 2006; 144(2): 217-22.
  25. Sak S, Uyanikoglu H, Incebiyik A, Incebiyik H, Hilali NG, Sabuncu T, et al. Associations of serum fetuin-A and oxidative stress parameters with polycystic ovary syndrome. Clin Exp Reprod Med 2018; 45(3): 116-21.
  26. Sulaiman MA, Al-Farsi YM, Al-Khaduri MM, Saleh J, Waly MI. Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women. Int J Womens Health 2018; 10: 763-71.
  27. Diba M, Seghatoleslam A, Namavari M, Assadi S, Vakili SN, Babaei Z, et al. Potential protective role of cyrtopodion scabrum in antioxidant parameters in serum and liver of rats with 5-FU-induced oxidative damage. Arch Razi Inst 2021; 76(1): 95-105.
  28. Tonelli C, Chio IIC, Tuveson DA. Transcriptional regulation by Nrf2. Antioxid Redox Signal 2018; 29(17): 1727-45.
  29. Kabel AM, Abd Elmaaboud MA, Albarraq AA. Ameliorative potential of omega 3 fatty acids and HMG-CoA reductase inhibitors on experimentally-induced non-alcoholic steatohepatitis. Prostaglandins Leukot Essent Fatty Acids 2015; 96: 1-9.
  30. Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sanchez-Perez P, Cadenas S, et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 2015; 6: 183-97.
  31. Kabel AM, Ashour AM, Omar MS, Estfanous RS. Effect of fish oil and telmisartan on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: The role of oxidative stress, transforming growth factor beta-1, and nuclear factor kappa B. Food Sci Nutr 2020; 8(9): 5149-59.