Silver Nanoparticles Biofabricated from Cinnamomum zeylanicum Reduce IL-6, IL-18, and TNF-ɑ in Female Rats with Polycystic Ovarian Syndrome

Document Type : Short Communication


1 Department of Physiology, Pharmacology and Biochemistry, College of Veterinary Medicine, University of Basrah, Iraq

2 Community Health Department, Technical Institute of Karbala, Al-Furat Al-Awsat Technical University, Karbala, Iraq


Polycystic ovarian, or stein leventhal, syndrome (PCOS) is an inflammatory disorder resulting in metabolic dysregulation and ovarian dysfunction as well as women’s infertility. Management of PCOS requires multiple approaches. This experimental study was sought to assess the influence of Cinnamomum zeylanicum (CZ) derived silver particles (AgNPs) on inflammatory cytokines in rats with PCOS.
In this experimental study, AgNPs were synthesized using CZ bark extract, and characterized by the scanning electron microscope (SEM) and atomic force microscope (AFM). Thirty female rats, rattus norvegicus, were grouped into five groups (6 animals/group). The experimental groups were vehicle control group (received 0.2 ml corn oil only), PCOS (received estradiol valerate of 4 mg/kg only), PCOS group received CZ extract (200 mg/kg), PCOS group received metformin (50 mg/kg) and PCOS group received AgNPs (3.53 mg/kg). After 30 days of treatment, serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukins-18 (IL-18), and 6 (IL-6) were measured using ELISA.
Significant elevation (P<0.05) was noted in TNF-α, IL-6, and IL-18 levels of the PCOS group when compared with findings in the control group (TNF-α: 250.4 ± 32.5 vs. 164.3 ± 34.4 ng/L, IL-6: 169.8 ± 9.4 vs. 77.0 ± 9.3 pg/ml, and IL-18: 45.9 ± 5.5 vs. 35.3 ± 4.1 ng/L). Importantly, AgNPs decreased all three inflammatory biomarkers in the treated group when compared with the PCOS group (TNF-α: 173.9 ± 31.2 vs. 250.4 ± 32.5 ng/L, IL-6: 133.7 ± 9.3 vs. 169.8 ± 9.4 pg/ml, and IL-18: 36.1 ± 6.2 vs. 45.9 ± 5.5 ng/L).
CZ-derived AgNPs may have an anti-inflammatory effect in PCOS rats by decreasing the concentrations of inflammatory cytokines TNF-α, IL-6 and IL-18.


  1. Al-Musawy S, Al-Saimary I, Flaifil M. Levels of cytokines profile in polycystic ovary syndrome. Med J Babylon. 2018; 15(2): 124-128.
  2. Sun J, Yuan Y, Cai R, Sun H, Zhou Y, Wang P, et al. An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials. BMJ Open. 2015; 5(3): 1-8.
  3. Zeng X, Xie Y, Liu Y, Long S, Mo Z. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020; 502: 214-221.
  4. Jensterle M, Kravos NA, Ferjan S, Goricar K, Dolzan V, Janez A. Long-term efficacy of metformin in overweight-obese PCOS: Longitudinal follow-up of retrospective cohort. Endocr Connect. 2020; 9(1): 44-54.
  5. Yildiz BO. Approach to the patient: contraception in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015; 100(3): 794-802.
  6. Moini Jazani A, Nasimi Doost Azgomi H, Nasimi Doost Azgomi A, Nasimi Doost Azgomi R. A comprehensive review of clinical studies with herbal medicine on polycystic ovary syndrome (PCOS). Daru. 2019; 27(2): 863-877.
  7. Hong L, Zhang Y, Wang Q, Han Y, Teng X. Effects of interleukin 6 and tumor necrosis factor-α on the proliferation of porcine thecainterna cells: possible role of these cytokines in the pathogenesis of polycystic ovary syndrome. Taiwan J Obstet Gynecol. 2016; 55(2): 183-187.
  8. Harwood HJ. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology. 2012; 63(1): 57-75.
  9. Thathapudi S, Kodati V, Erukkambattu J, Katragadda A, Addepally U, Hasan Q. Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study. Genet Test Mol Biomarkers. 2014; 18(9): 605-609.
  10. Fulghesu AM, Sanna F, Uda S, Magnini R, Portoghese E, Batetta B. IL-6 serum levels and production is related to an altered immune response in polycystic ovary syndrome girls with insulin resistance. Mediators Inflamm. 2011; 2011: 389317.
  11. Gunawardena D, Karunaweera N, Lee S, van Der Kooy F, Harman DG, Raju R, et al. Anti-inflammatory activity of cinnamon (C. zeylanicum and C. cassia) extracts–identification of E-cinnamaldehyde and o-methoxy cinnamaldehyde as the most potent bioactive compounds. Food Funct. 2015; 6(3): 910-919.
  12. Balasooriya ER, Jayasinghe CD, Jayawardena UA, Ruwanthika RW, Mendis de Silva R, Udagama PV. Honey mediated green synthesis of nanoparticles: new era of safe nanotechnology. J Nanomater. 2017; ID 5919836.
  13. Vijayakumar S, Divya M, Vaseeharan B, Chen J, Biruntha M, Silva LP, et al. Biological compound capping of silver nanoparticle with the seed extracts of blackcumin (nigella sativa): a potential antibacterial, antidiabetic, anti-inflammatory, and antioxidant. J Inorg Organomet Polym Mater. 2020; 31: 624-635.
  14. Jasim NA, Al-Gasha’a FA, Al-Marjani MF, Al-Rahal AH, Abid HA, Al-Kadhmi NA, et al. ZnO nanoparticles inhibit growth and biofilm formation of vancomycin-resistant S. aureus (VRSA). Biocatal Agric Biotechnol. 2020; 29: 101745.
  15. Loo YY, Rukayadi Y, Nor-Khaizura MA, Kuan CH, Chieng BW, Nishibuchi M, et al. In Vitro antimicrobial activity of green synthesized silver nanoparticles against selected gram-negative foodborne pathogens. Front Microbiol. 2018; 9: 1555.
  16. Tyavambiza C, Elbagory A, Madiehe M, Madimabe A, Meyer M, Meyer S. The antimicrobial and anti-Inflammatory effects of silver nanoparticles synthesised from cotyledon orbiculata aqueous extract. Nanomaterials (Basel). 2021; 11(5): 1343.
  17. Agarwal H, Nakara A, Shanmugam VK. Anti-inflammatory mechanism of various metal and metal oxide nanoparticles synthesized using plant extracts: a review. Biomed Pharmacother. 2019; 109: 2561-2572.
  18. Alwan SH, Al-Saeed MH. Biosynthesized silver nanoparticles (using Cinnamomum zeylanicum bark extract) improve the fertility status of rats with polycystic ovarian syndrome. Biocatal Agric Biotechnol. 2021; 38: 102217.
  19. Jelodar G, Masoomi S, Rahmanifar F. Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model. Iran J Basic Med Sci. 2018; 21(6): 645-650.
  20. Anbu AS, Venkatachalam P. Biological macromolecule cross linked TPP–chitosan complex: a novel nanohybrid for improved ovulatory activity against PCOS treatment in female rats. RSC Adv. 2016; 6(97): 94301-94313.
  21. Alwan S, Al-Saeed M, Abid H. Safety assessment and biochemical evaluation of the effect of biogenic silver nanoparticles (using bark extract of C. zeylanicum) on Rattus norvegicus rats. Baghdad J Biochem Appl Biol Sci. 2021; 2(03): 133-145.
  22. Gao L, Gu Y, Yin X. High serum tumor necrosis factor-alpha levels in women with polycystic ovary syndrome: a meta-analysis. PLoS One. 2016; 11(10): 1-18.
  23. Ebejer K, Calleja-Agius J. The role of cytokines in polycystic ovarian syndrome. Gynecol Endocrinol. 2013; 29(6): 536-540.
  24. Jabbour HN, Sales KJ, Catalano RD, Norman JE. Inflammatory pathways in female reproductive health and disease. Reproduction. 2009; 138(6): 903-919.
  25. Greenfeld CR, Roby KF, Pepling ME, Babus JK, Terranova PF, Flaws JA. Tumor necrosis factor (TNF) receptor type 2 is an important mediator of TNF alpha function in the mouse ovary. Biol Reprod. 2007; 76(2): 224-231.
  26. Wang YX, Zhu WJ. Evaluation of adiponectin, resistin, IL-6, TNF-α in obese and non-obese women with polycystic ovary syndrome. J Reprod Contracept. 2012; 23(4): 237-244.
  27. Tung YT, Chua MT, Wang SY, Chang ST. Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs. Bioresour Technol. 2008; 99(9): 3908-3913.
  28. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014; 5: 461.
  29. Prasad SR, Elango K, Chellakumari SD, Dharani S. Preparation, characterization and anti- inflammatory activity of chitosan stabilized silver nanoparticles article. Res J Pharma Dos Forms Tech. 2013; 5(3): 161-167.
  30. Kumararaja G, Sundaraganapathy R, Constantine I, Vijayalakshmi V, Abdur RSF. Comparative studies on synthesized silver nanoparticles using Artemisia vulgaris Linn., and Cinnamomum zeylanicum Nees., for their antifungal activity. J Pharm Sci Res. 2019; 11(7): 2558-2565.