International Journal of Drug Delivery Technology
Volume 15, Issue 3

Synergistic Potential of Ecklonia cava and Oral Contraceptives in Managing Polycystic Ovary Syndrome: Clinical and Biochemical Evaluation 

Asmaa Najm Abd1, Ahmed R Abu‑Raghif 2, Lubna Amer Al-Anbari3, Hayder Ridha-Salman4* 

1Diyala University, College of Medicine, Department of Pharmacology, Diyala, Iraq

2Al-Nahrain University, College of Medicine, Department of Pharmacology, Baghdad, Iraq

3High Institute for Infertility Diagnosis and Assisted Reproductive Technologies (ART), Al-Nahrain University, Baghdad, Iraq

4Al-Mustaqbal University, College of Pharmacy, Hillah-51001, Babylon, Iraq

Received: 24th Jul, 2025; Revised: 18th Aug, 2025; Accepted: 2nd Sep, 2025; Available Online: 25th Sep, 2025

ABSTRACT

Background: Polycystic Ovary Syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age, influencing the endocrine, reproductive system, and metabolic processes.

Objectives: To evaluate the anti-inflammatory and hormonal modulation effects of Ecklonia cava in PCOS patients.

Methods: In this Randomized controlled study, 50 patients were diagnosed with polycystic ovary syndrome. Their age range (18-40 years) was equally allocated into two groups. The Control group received   Diane- 35 (2mg cyproterone acetate/35 Mg ethinyl estradiol) once daily for 3 cycles, and the interventional group received a combination of Diane- 35 plus 300 mg of Ecklonia cava once daily for 3 months. Parameters assessed before and after treatments course include: serum LH and FSH, oLH/FSH ratio, free testosterone, leptin HBA1c, IL-8, IL-10.

Results: After 3 months, there was a significant reduction in the weight and waist circumference in the study group in comparison with the control group, with a p-value ≤0.05; significant improvement in LH, FSH, LH/FSH, Free testosterone and leptin hormone, in addition significant reduction in IL-8, and increase IL-10 level.

Conclusions: The addition of Eckonia cava to the Diane- 35 in the treatment of PCOS patients gives promising synergistic effects in the regulation of clinical and biochemical parameters in PCOS. Patient

Keywords: Polycystic ovary syndrome, Ecklonia cava, Obesity, Hba1c, Free Testosterone, IL-8, IL-10.

How to cite this article: Asmaa Najm Abd, Ahmed R Abu‑Raghif, Lubna Amer Al-Anbari, Hayder Ridha-Salman. Synergistic Potential of Ecklonia cava and Oral Contraceptives in Managing Polycystic Ovary Syndrome: Clinical and Biochemical Evaluation. International Journal of Drug Delivery Technology. 2025;15(3):925-33. doi: 10.25258/ijddt.15.3.3

REFERENCES

  1. Hussein ZA, Majeed MJ, Al-Anbari LA. Impact of Myo-Inositol-Chiro Inositol combination on the improvement of polycystic ovary syndrome condition. Med J Babylon. 2024;21(4):785–9. doi:10.4103/MJBL.MJBL_1026_23.
  2. Garg A, Patel B, Abbara A, Dhillo WS. Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf). 2022;97(2):156–64. doi:10.1111/cen.14704.
  3. 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;20:25. doi:10.1186/s43042-019-0031-4.
  4. Yildiz BO, Bolour S, Woods K, Moore A, Azziz R. Visually scoring hirsutism. Hum Reprod Update. 2010;16(1):51–64. doi:10.1093/humupd/dmp024.
  5. Alhussien ZA, Mossa HAL, Abood MS. The Effect of L-carnitine on Apoptotic Markers (Annexin V and Clusterin) in Polycystic Ovarian Syndrome Women undergoing ICSI. International Journal of Drug Delivery Technology. 2022;12(4):1682-6.
  6. Naji ME, Gatea FK, Ali KA, Raghif ARA. Effect of Convolvulus arvensis ethanolic extract on testosterone-induced alopecia in mice. Int J Drug Deliv Technol. 2022 Jul-Sep;12(3).
  7. Hassan SF, Abu Raghif AR, Kadhim EJ, Ridha-Salman H, Abbas AH. Phytochemical composition, antioxidant, antihyperlipidemic, and hepatoprotective effects of phenolic components of Iraqi sumac (Rhus coriaria) Eur J Clin Exp Med. 2025;23(3):1-24.
  8. Abu-Raghif AR, Sahib HB, Abbas SN. Anti-hyperlipidemic effect of vitex agnus castus extracts in mice. International Journal of Pharmaceutical Sciences Review and Research. 2015;35(2):120-5.
  9. Mortada R, Kallail KJ, Dong F, Karakas S. HbA1c in patients with polycystic ovary syndrome: a potential marker of inflammation. J Reprod Infertil. 2015 Oct-Dec;16(4):203-6. PMID: 27110518; PMCID: PMC4819209.
  10. Dawood, M.H , Raghif, A.R.A., and Yaseen, Y.A. Effects of coenzyme Q10 administration on glucose homeostasis parameters in prediabetic patients.Journal of Pharmaceutical Sciences and Research, 2017, 9(11), pp. 2274–227.
  11. Jaafar FR, Attarbashee RK, Abu-Raghif AR, Ridha-Salman H. Gemifloxacin ameliorates acetic acid-induced ulcerative colitis via modulation of inflammatory, oxidative, and adhesive biomarkers and histopathological changes in rats. Journal of Molecular Histology. 2025;56(4):250.
  12. Abu-Raghif AR, AL Kazzaz AM, Fadheel QJ. A comparative study of the effect of thyme and Calcium with Vitamin D3 in treatment of postmenopausal women with osteoporosis. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2016;9(5):260-8
  13. Raheem AK, Abu-Raghif AR, Abbas AH, Ridha-Salman H, Oubaid EN. Quercetin mitigates sepsis-induced renal injury via inhibiting inflammatory and oxidative pathways in mice. Journal of Molecular Histology. 2025;56(3):184.
  14. Delitala AP, Capobianco G, Delitala G, Cherchi PL, Dessole S. Polycystic ovary syndrome, adipose tissue, and metabolic syndrome. Arch Gynecol Obstet. 2017 Sep;296(3):405-19. doi: 10.1007/s00404-017-4429-2. PMID: 28643028.
  15. Sadeghi HM, Adeli I, Calina D, Docea AO, Mousavi T, Daniali M, et al. Polycystic ovary syndrome: a comprehensive review of pathogenesis, management, and drug repurposing. Int J Mol Sci. 2022 Jan 6;23(2):583. doi: 10.3390/ijms23020583. PMID: 35054768; PMCID: PMC8775814.
  16. Heo SJ, Jeon YJ. Protective effect of phlorotannins derived from Ecklonia cava against high glucose-induced oxidative stress in human umbilical vein endothelial cells. Toxicol In Vitro. 2009;23(5):874–81.
  17. Wijesinghe WAJP, Ko SC, Jeon YJ. Protective effect of polyphenol-rich extract of Ecklonia cava against oxidative stress-induced DNA damage in kidney epithelial cells. Mar Biotechnol. 2011;13(5):820–9.
  18. Shin HC, Hwang HJ, Kang KY, Ahn YJ, Kim JH, Lee SH. Anti-obesity effects of Ecklonia cava extract in high-fat diet-induced obese rats. Mar Drugs. 2012;10(2):254–65.
  19. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.
  20. Shin HC, Hwang HJ, Kang KW, Lee BH, Lee SH. Anti-obesity effect of extract from Ecklonia cava in diet-induced obese rats. Journal of Medicinal Food. 2012;15(2):147-54.
  21. Park MH, Jeong HJ, Yang GY, Choi YH, Choi SH, Lee SH. Effects of phlorotannins from Ecklonia cava on the inhibition of lipid accumulation in 3T3-L1 adipocytes. Phytother Res. 2013;27(4):454-459.
  22. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961 Nov;21(11):1440-7. doi: 10.1210/jcem-21-11-1440.
  23. Jung HA, Jung MJ, Kang SS, Kang JY, Kim SY, Choi JS. Beneficial effects of Ecklonia cava polyphenol extract on body composition and metabolic parameters in overweight Korean adults: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2012;26(10):1542–1547. doi:10.1002/ptr.4657.
  24. Lee SH, Park MH, Heo SJ, Kang SM, Ko SC, Han JS, et al. Dieckol isolated from Ecklonia cava regulates the gut microbiota and reduces visceral fat in diet-induced obese rats. J Med Food. 2019;22(2):146–153. doi:10.1089/jmf.2018.0034.
  25. Hussein ZA, Majeed MJ, Al-Anbari LA, Al‐Naqeeb SAR. The Association between the Levels of Phosphodiesterase 9, Insulin-like peptide 5 and Obesity in Women. Al-Kindy Col. Med. J [Internet]. 2024 Aug. 1 [cited 2025 Jun. 3];20(2):117-21. Available from: https://jkmc.uobaghdad.edu.iq/index.php/MEDICAL/article/view/1140
  26. Sraibit Abbod M, Al-Jawad FH, Anoze AA, Ali Jawad M, Qasim BJ. Antiatherosclerotic effect of L-thyroxine and verapamil combination on thoracic aorta of hyperlipidemic rabbits. International Journal of Pharmaceutical Sciences Review and Research. 2014;27(1):254-60.
  27. Azziz R, Carmina E, Chen Z, Dunaif A, Laven J, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016; 2:16057.
  28. Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Tapanainen JS. Metformin versus ethinyl estradiol–cyproterone acetate in the treatment of polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2000;85(3):296–301.
  29. Kang K-A, Lee KH, Chae S, Zhang R, Jung M-S, Ham Y-M, et al. Ecklonia cava attenuates oxidative stress induced cell damage in human keratinocytes via antioxidant activity. J Ethnopharmacology. 2013;146(3):853-9.
  30. Shibata T, Kawaguchi S, Yamaguchi K, Tanaka R, Nakano T, Hoshino T. Biological activities of Ecklonia cava: antioxidant, anti-inflammatory, and anti-cancer effects. Mar Drugs. 2017;15(2):50.
  31. Randall VA. Androgens and hair growth. Dermatol Ther. 2008;21(5):314-28.
  32. Sharquie KE, Turki KM, Abu-Raghif AR, Al-Geboori HG. Oxidative stress in patients with premature hair grayness. Saudi Medical Journal. 2005;26 (8):1310-1.
  33. Cooney LG, Dokras A. Use of complementary and alternative medicines among women with polycystic ovary syndrome: a systematic review. Fertil Steril. 2014;102(3):831-40.
  34. Abu-Raghif A, Mahdi Z. In vivo study of the effect of 5 and 10% nebivolol cream on hair growth in mice models. Int J Drug Del Technol. 2022;12(3):1148-55.
  35. Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Tapanainen JS. Metformin versus ethinyl estradiol–cyproterone acetate in the treatment of polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2000;85(3):296–301.
  36. Kang K-A, Lee KH, Chae S, Zhang R, Jung M-S, Ham Y-M, et al. Ecklonia cava attenuates oxidative stress induced cell damage in human keratinocytes via antioxidant activity. J Ethnopharmacol. 2013;146(3):853-9.
  37. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrom. Fertil Steril. 2018;110(3):364-379.
  38. Kim JH, Lee JH, Lee SK, et al. Ecklonia cava extract improves polycystic ovary syndrome by modulating inflammatory markers and hormone levels in a letrozole-induced rat model. Phytother Res. 2019;33(4):1065-75. doi:10.1002/ptr.6307.
  39. Jawad HH, Al-Anbari L, Abbood M. Assessment of the relationship of basal serum anti mullerian hormone levels and maternal age with pregnancy out come in patients undergoing icsi. Annals of Tropical Medicine and Public Health. 2020;23(4).
  40. Panidis D, Tziomalos K, Misichronis G, et al. Oral contraceptives in PCOS: impact on metabolic profile and androgen levels. Eur J Endocrinol. 2010;162(2):283–290.
  41. Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356(6):551–566.
  42. Lee SH, Jeon YJ. Anti-diabetic effects of brown algae-derived phlorotannins, marine polyphenols through diverse mechanisms. Fitoterapia. 2013;86:129–136.
  43. Abunaila RsH, Al-Anbari LA, Abbood MS. The effects of adding Gonadotropin-releasing Hormone antagonist on cycle characteristics and pregnancy rate in stimulated Intrauterine Insemination (IUI) cycle. International Journal of Research in Pharmaceutical 2020;11:3053-60.
  44. Ali ZH, Mossa HAL, Abood MS. Evaluation of Endometrial Receptivity and Pregnancy Outcome in view of Assessment of Serum and Follicular Fluid Level of CD44 Following Administration of Hyaluronic Acid to Infertile Women. Pharmacologyonline. 2021;3:536-44.
  45. Shin HC, Hwang HJ, Kang SG, et al. The effects of Ecklonia cava extract on sexual behavior of male rats. Korean J Pharmacogn. 2012;43(3):201–206.
  46. Kang KA, Lee KH, Chae S, et al. Effect of phlorotannins on testosterone production and reproductive function in aged mice. Biomed Pharmacother. 2015;69:373–380.
  47. Panidis D, Kourtis A, Farmakiotis D, et al. Serum leptin and insulin levels in overweight and normal-weight women with PCOS. Hum Reprod. 2003;18(9):1790–1796.
  48. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004;351(10):987–997.
  49. Ibáñez L, Potau N, Marcos MV, et al. Insulin sensitivity improves after two months of antiandrogen treatment in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab. 2000;85(7):2353–2356.
  50. Heo SJ, Park EJ, Lee KW, Jeon YJ. Antioxidant activities of enzymatic extracts from brown seaweeds. Bioresource Technol. 2005;96(14):1613–1623.
  51. Lee SH, Jeon YJ. Anti-diabetic effects of brown algae-derived phlorotannins. Fitoterapia. 2013; 86:129–136.
  52. Luty RS, Al-Zubaidy AA, Malik AS, Ridha-Salman H, Abbas AH. Protective effect of orientin on diabetic nephropathy in rat models of high-fat diet and streptozotocin-induced diabetes. Naunyn-Schmiedeberg's Archives of Pharmacology. 2025.
  53. Diamanti-Kandarakis E, Papa Vassiliou AG. Molecular mechanisms of insulin resistance in PCOS. Trends Mol Med. 2006;12(7):324–332.
  54. Kang MC, Wijesinghe WAJP, Lee SH, et al. Antidiabetic effects of marine algae-derived compounds. J Med Food. 2011;14(5):512–520.
  55. Luty RS, Abbas SF, Haji SA, Ridha-Salman H. Hepatoprotective effect of catechin on rat model of acetaminophen-induced liver injury. Comparative Clinical Pathology. 2025.
  56. Thammer MR, Sahib HB, Ridha-Salman H. Skin Healing Potential of Bioactive Components from Lycoperdonosis lividum Mushroom Versus β-Sitosterol in Rat Model of Burn Wounds. Microsc Res Tech. 2025.
  57. González F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300–305.
  58. Oróstica L, Vega M, García V, et al. Proinflammatory environment and role of TNF-α in local alterations of granulosa cells from women with PCOS. Reproduction. 2016;152(4):477–485.
  59. Vural B, Caliskan E, Turkoz E, et al. Evaluation of the effect of oral contraceptive treatment on serum cytokines and lymphocyte subsets in PCOS. Eur J Obstet Gynecol Reprod Biol. 2005;118(2):222–227.
  60. Kluge M, Lange U, Schmidt E, et al. Influence of oral contraceptives on markers of inflammation. Contraception. 2010;82(3):235–239.
  61. Park EJ, Pezzuto JM. Anti-inflammatory and anti-cancer potential of marine algae-derived compounds. Mini Rev Med Chem. 2013;13(2):129–137.
  62. Abdul-Majeed ZM, Al-atrakji MQYMA, Ridha-Salman H. Cranberry extract attenuates indomethacin-induced gastriculcer in rats via its potential atioxidant and anti-inflammatory effects. J Mol Histol 2025;56(4):206.
  63. Abbas AH, Abbood MS, Ridha-Salman H, Fakhri SA, Abbas ZH, Al-Athari AJH. Suppressive effect of topical moxifloxacin on imiquimod-induced model of psoriasis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2025; 399:1–20 DOI: 10.1007/s00210-025-04317-2.
  64. Ali BF, Abu-Raghif AR, Ridha-Salman H, Al-Athari AJH. Vildagliptin topical ointment: an effective treatment for imiquimod-induced psoriasis in mice. Journal of Molecular Histology. 2025;56(3):143.
  65. Escobar-Morreale HF, Luque-Ramírez M, Gonzalez F. Circulating inflammatory markers in PCOS: a systematic review and meta-analysis. Fertil Steril. 2011;95(3):1048–1058.
  66. Repaci A, Gambineri A, Pasquali R. The role of low-grade inflammation in PCOS. Mol Cell Endocrinol. 2011;335(1):30–41.