Vet Med - Czech, 2025, 70(6):203-217 | DOI: 10.17221/116/2024-VETMED
Antioxidant and cytokine modulation in PCOS rats protected with probiotics, myo-inositol, and herbal extractsOriginal Paper
- 1 Department of Biomedical Sciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
- 2 Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
- 3 National Center for the Prevention & Control of Plants Pests & Animal Diseases, Buraydah, Qassim Region, Saudi Arabia
- 4 Department of Pathology and Laboratory Diagnosis, Collage of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
This study investigated the pathophysiology of polycystic ovarian syndrome (PCOS) and evaluated the protective effects of various treatments in immature female Wistar rats (N = 48). The rats were divided into 6 groups: Olive oil injection (negative control, G1); testosterone propionate (TP)-induced PCOS (G2); probiotic + TP (G3); myo-inositol (myo-ins) + TP (G4); U. dioica extract + TP (G5); W. somnifera extract + TP (G6). The body weight, body weight gain, and percentage gain were measured weekly and then transformed using the base-10 logarithm (log10). TNF-α, IL-4, IL-10, and IL-17 were weekly measured using ELISA kits. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were analysed in the serum and liver extracts. The W. somnifera significantly reduced the TNF-α levels (P < 0.01). The probiotic and myo-ins significantly elevated the IL-10 levels (P < 0.01). Both plant extracts moderately restored the IL-10 levels. The probiotic and U. dioica administration significantly reduced the IL-17 levels (P < 0.01). The W. somnifera administration also decreased the IL-17 levels, though the effect was less pronounced than that of U. dioica. The probiotic, myo-ins, and W. somnifera groups exhibited enhanced CAT activity (P < 0.05). W. somnifera showed significant increases in the SOD and GSH-Px activities (P < 0.01), showing the most dramatic improvement. The use of these four treatments as a monotherapy in this study resulted in different changes. Therefore, further investigation is necessary to evaluate the protective effects of combining duos or trios of these treatments against this disease.
Keywords: antioxidants; ELISA; immunity; myo-inositol; polycystic ovarian syndrome
Received: December 15, 2024; Revised: April 14, 2025; Accepted: May 5, 2025; Prepublished online: June 27, 2025; Published: June 30, 2025 Show citation
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References
- Adelakun SA, Babatunde O, Chinazo C C, Arowosegbe OA, Adisa DO. Histomorphological and histomorphometric evaluation of the therapeutic role of sulforaphane on the hypothalamic-pituitary-ovarian axis in polycystic ovary syndrome rats via its potential anti-inflammatory and antioxidant activities. Med Omics. 2024 Mar;10:100029.
Go to original source...
- Adeyanju OA, Falodun TO, Michael OS, Soetan OA, Oyewole AL, Agbana RD. Spironolactone reversed hepato-ovarian triglyceride accumulation caused by letrozole-induced polycystic ovarian syndrome: Tissue uric acid - A familiar foe. Naunyn Schmiedebergs Arch Pharmacol. 2020 Jun;393(6):1055-66.
Go to original source...
Go to PubMed...
- Adwas AA, Elsayed A, Azab AE, Quwaydir FA. Oxidative stress and antioxidant mechanisms in human body. J Appl Biotechnol Bioeng. 2019 Feb;6(1):43-7.
Go to original source...
- Ajibare AJ, Akintoye OO, Famurewa AC, Folawiyo MA, Bamisi OD, Asuku AO, Oyegbola OE, Akintayo CO, Olofinbiyi BA, Omotuyi OI. Synergistic action of virgin coconut oil and clomiphene in reversing endocrine dysregulation in letrozole-model of polycystic ovarian syndrome in rats: Role of Nrf2/HMOX-1 pathway. J Med Food. 2023 Sep;26(9):683-91.
Go to original source...
Go to PubMed...
- Antonowski T, Osowski A, Szczesny D, Szablinska-Piernik J, Juskiewicz J, Lahuta L, Rynkiewicz A, Wojtkiewicz J. Pharmacokinetics of myo-inositol in a wistar rat animal model. Int J Mol Sci. 2022 Sep 24;23(19):11246.
Go to original source...
Go to PubMed...
- Arefhosseini S, Roshanravan N, Asghari S, Tutunchi H, Ebrahimi-Mameghani M. Expression of inflammatory genes, WBC-derived inflammatory biomarkers and liver function indices: Effects of myo-inositol supplementation in obese patients with NAFLD. J Funct Foods. 2023 May;104:105524.
Go to original source...
- Awad NYEE. Therapeutic potentials of ashwagandha extract on the toxic effect of benzo(a) pyrene in male rats. Res J Spec Edu. 2022 Jul;(69):45-64.
Go to original source...
- Bandariyan E, Mogheiseh A, Ahmadi A. The effect of lutein and Urtica dioica extract on in vitro production of embryo and oxidative status in polycystic ovary syndrome in a model of mice. BMC Complement Med Ther. 2021 Feb 8;21(1):55.
Go to original source...
Go to PubMed...
- Bevilacqua A, Bizzarri M. Physiological role and clinical utility of inositols in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016 Nov;37:129-39.
Go to original source...
Go to PubMed...
- Bevilacqua A, Dragotto J, Giuliani A, Bizzarri M. Myo-inositol and D-chiro-inositol (40 : 1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol. 2019 Jun;234(6):9387-98.
Go to original source...
Go to PubMed...
- Bhargavan D, Deepa B, Shetty H, Krishna AP. The protective effect of Withania somnifiera against oxidative damage caused by ethanol in the testes of adult male rats. Int J Basic Clin Pharmacol. 2015;4(6):1104-9.
Go to original source...
- Bhusal KK, Magar SK, Thapa R, Lamsal A, Bhandari S, Maharjan R, Shrestha J. Nutritional and pharmacological importance of stinging nettle (Urtica dioica L.): A review. Heliyon. 2022;8(6).
Go to original source...
Go to PubMed...
- Chaudhari NK, Nampoothiri LP. Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model. Horm Mol Biol Clin Investig. 2017 Feb 1;29(2):71-7.
Go to original source...
Go to PubMed...
- Chitra V, Dhivya DP. Role of herbals in the management of polycystic ovarian syndrome and its associated symptoms. Int J Herb Med. 2017;5(5):125-31.
- Dinicola S, Unfer V, Facchinetti F, Soulage CO, Greene ND, Bizzarri M, Lagana AS, Chan SY, Bevilacqua A, Pkhaladze L, Benvenga S, Stringaro A, Barbaro D, Appetecchia M, Aragona C, Bezerra Espinola MS, Cantelmi T, Cavalli P, Chiu TT, Copp AJ, D'Anna R, Dewailly D, Di Lorenzo C, Diamanti-Kandarakis E, Hernandez Marin I, Hod M, Kamenov Z, Kandaraki E, Monastra G, Montanino Oliva M, Nestler JE, Nordio M, Ozay AC, Papalou O, Porcaro G, Prapas N, Roseff S, Vazquez-Levin M, Vucenik I, Wdowiak A. Inositols: From established knowledge to novel approaches. Int J Mol Sci. 2021 Sep 30;22(19):10575.
Go to original source...
Go to PubMed...
- Dutta R, Khalil R, Green R, Mohapatra SS, Mohapatra S. Withania somnifera (ashwagandha) and withaferin A: Potential in integrative oncology. Int J Mol Sci. 2019 Oct 25;20(21):5310.
Go to original source...
Go to PubMed...
- Dutta S, Henkel R, Sengupta P, Agarwal A. Physiological role of ROS in sperm function. In: Parekattil SJ, Esteves SC, Agarwal A, editors. Male infertility: Contemporary clinical approaches, andrology, ART and antioxidants. Cham: Springer; 2020. p. 337-45.
Go to original source...
- Dutta S, Sengupta P, Izuka E, Menuba I, Nwagha U. Oxidative and nitrosative stress and female reproduction: Roles of oxidants and antioxidants. J Integr Sci Technol. 2024 Nov 6;12(3):1-11.
Go to original source...
- Ejtahed HS, Angoorani P, Soroush AR, Atlasi R, Hasani-Ranjbar S, Mortazavian AM, Larijani B. Probiotics supplementation for the obesity management: A systematic review of animal studies and clinical trials. J Funct Foods. 2019 Jan;(52):228-42.
Go to original source...
- Ejtahed HS, Angoorani P, Soroush AR, Siadat SD, Shirzad N, Hasani-Ranjbar S, Larijani B. Our little friends with big roles: Alterations of the gut microbiota in thyroid disorders. Endocr Metab Immune Disord Drug Targets. 2020;20(3):344-50.
Go to original source...
Go to PubMed...
- Erejuwa OO, Gurtu S, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, Salleh MS. Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats. Int J Vitam Nutr Res. 2010 Jan;80(1):74-82. Erratum in: Int J Vitam Nutr Res. 2011 Nov;81(6):346.
Go to original source...
Go to PubMed...
- Escobar-Morreale HF, Luque-Ramirez M, Gonzalez F. Circulating inflammatory markers in polycystic ovary syndrome: A systematic review and metaanalysis. Fertil Steril. 2011 Mar 1;95(3):1048-58.e1-2.
Go to original source...
Go to PubMed...
- Facchinetti F, Bizzarri M, Benvenga S, D'Anna R, Lanzone A, Soulage C, Di Renzo GC, Hod M, Cavalli P, Chiu TT, Kamenov ZA, Bevilacqua A, Carlomagno G, Gerli S, Oliva MM, Devroey P. Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in obstetrics and gynecology: The link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:72-6.
Go to original source...
Go to PubMed...
- Greff D, Juhasz AE, Vancsa S, Varadi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirady P, Acs N, Varbiro S, Horvath EM. Inositol is an effective and safe treatment in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023 Jan 26;21(1):10.
Go to original source...
Go to PubMed...
- Gulan T, Yeernuer T, Sui S, Mayinuer N. A rat model of maternal polycystic ovary syndrome shows that exposure to androgens in utero results in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn rat. Med Sci Monit. 2019 Dec 9;25:9377-91.
Go to original source...
Go to PubMed...
- Heimark D, McAllister J, Larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr J. 2014;61(2):111-7.
Go to original source...
Go to PubMed...
- Krishna KV, Sharma A, Karthickeyan Krishnan A, Javalgikar DNRK, Sahoo NK, Bagal DK, Pandey K, Vigneswari S. Polycystic ovarian syndrome: A brief review on the role of allopathic and herbal treatment. J Cardiovasc Dis Res. 2023 Aug;14(8):351-68.
- Lee YJ, Lee SY. Maclurin exerts anti-cancer effects in human osteosarcoma cells via prooxidative activity and modulations of PARP, p38, and ERK signaling. IUBMB Life. 2021 Aug;73(8):1060-72.
Go to original source...
Go to PubMed...
- Liu J, Qu T, Li Z, Yu L, Zhang S, Yuan D, Wu H. Serum kisspeptin levels in polycystic ovary syndrome: A meta-analysis. J Obstet Gynaecol Res. 2021 Jun;47(6):2157-65.
Go to original source...
Go to PubMed...
- Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018 Aug 20;16(1):80.
Go to original source...
Go to PubMed...
- Mazloom BF, Edalatmanesh MA, Hosseini SE. Gallic acid reduces inflammatory cytokines and markers of oxidative damage in a rat model of estradiol-induced polycystic ovary. Comp Clin Pathol. 2019 Feb 15;28:1281-6.
Go to original source...
- Mohammadi M. Oxidative stress and polycystic ovary syndrome: A brief review. Int J Prev Med. 2019 May 17;10(1):1-7.
Go to original source...
Go to PubMed...
- Montanino Oliva M, Buonomo G, Calcagno M, Unfer V. Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women. J Ovarian Res. 2018 May 10;11(1):38.
Go to original source...
Go to PubMed...
- Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family - Balance between agonists and antagonists in inflammatory diseases. Cytokine. 2015 Nov;76(1):25-37.
Go to original source...
Go to PubMed...
- Popovic M, Sartorius G, Christ-Crain M. Chronic low-grade inflammation in polycystic ovary syndrome: Is there a (patho)-physiological role for interleukin-1? Semin Immunopathol. 2019 Jul;41(4):447-59.
Go to original source...
Go to PubMed...
- Pundir J, Psaroudakis D, Savnur P, Bhide P, Sabatini L, Teede H, Coomarasamy A, Thangaratinam S. Inositol treatment of anovulation in women with polycystic ovary syndrome: A meta-analysis of randomised trials. BJOG. 2018 Feb;125(3):299-308.
Go to original source...
Go to PubMed...
- Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, Smolarczyk R, Meczekalski B. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7):3789.
Go to original source...
Go to PubMed...
- Ryssdal M, Vanky E, Stokkeland LMT, Jarmund AH, Steinkjer B, Lovvik TS, Madssen TS, Iversen AC, Giskeodegard GF. Immunomodulatory effects of metformin treatment in pregnant women with PCOS. J Clin Endocrinol Metab. 2023 Aug 18;108(9):e743-53.
Go to original source...
Go to PubMed...
- Saiyed A, Jahan N, Makbul SAA, Ansari M, Bano H, Habib SH. Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats. Integr Med Res. 2016 Dec;5(4):293-300.
Go to original source...
Go to PubMed...
- Sengupta P, Dutta S, Chhikara BS. Bioorthogonal chemistry in the reproductive medicine. Chem Biol Lett. 2023 Apr;10(3):545.
- Sengupta P, Dutta S, Hassan MF. Polycystic ovary syndrome (PCOS) and oxidative stress. J Integr Sci Technol. 2024 Mar 11;12(3):752.
Go to original source...
- Shorakae S, Ranasinha S, Abell S, Lambert G, Lambert E, de Courten B, Teede H. Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS. Clin Endocrinol (Oxf). 2018 Nov;89(5):628-33.
Go to original source...
Go to PubMed...
- Soujanya S, Mekala L, Doppalapudi MAD, Reddy AG, Rao SR. Ameliorative effect of Withania somnifera against imidacloprid induced alterations in oestrous cycle of female Albino Wistar rats. Indian J Pharm Sci. 2022 Mar-Apr;84(2):436-50.
Go to original source...
- Suvarna SK, Layton C, Bancroft JD. Theory and practice of histological techniques. 8th ed. Churchill: Elsevier Health Sciences; 2018. 584 p.
- Taheri Y, Quispe C, Herrera-Bravo J, Sharifi-Rad J, Ezzat SM, Merghany RM, Shaheen S, Azmi L, Prakash Mishra A, Sener B, Kilic M, Sen S, Acharya K, Nasiri A, Cruz-Martins N, Tsouh Fokou PV, Ydyrys A, Bassygarayev Z, Dastan SD, Alshehri MM, Calina D, Cho WC. Urtica dioica-derived phytochemicals for pharmacological and therapeutic applications. Evid Based Complement Alternat Med. 2022 Feb 24;2022:4024331.
Go to original source...
Go to PubMed...
- Talaat RM, Mohamed YA, Mohamad EH, Elsharkawy M, Guirgis AA. Interleukin 10 (- 1082 G/A) and (- 819 C/T) gene polymorphisms in Egyptian women with polycystic ovary syndrome (PCOS). Meta Gene. 2016 Aug 3;9:254-8.
Go to original source...
Go to PubMed...
- Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-79.
Go to original source...
Go to PubMed...
- Uckan K, Demir H, Turan K, Sarikaya E, Demir C. Role of oxidative stress in obese and nonobese PCOS patients. Int J Clin Pract. 2022 Feb 9;2022:4579831.
Go to original source...
Go to PubMed...
- Upton R. Stinging nettles leaf (Urtica dioica L.): Extraordinary vegetable medicine. J Herbal Med. 2013 Mar;3(1):9-38.
Go to original source...
- Vasyukova E, Zaikova E, Kalinina O, Gorelova I, Pyanova I, Bogatyreva E, Vasilieva E, Grineva E, Popova P. Inflammatory and anti-inflammatory parameters in PCOS patients depending on body mass index: A case-control study. Biomedicines. 2023 Oct 14;11(10):2791.
Go to original source...
Go to PubMed...
- Wang L, Zhou J, Gober HJ, Leung WT, Huang Z, Pan X, Li C, Zhang N, Wang L. Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype. Biomed Pharmacother. 2021 Jan;133:110958.
Go to original source...
Go to PubMed...
- Wang Y, Zhu W. Evaluation of adiponectin, resistin, IL-6, TNF-α in obese and non-obese women with polycystic ovary syndrome. J Reprod Contracep. 2012 Dec;23(4):237-44.
Go to original source...
- Xia Q, Wang W, Liu Z, Xiao J, Qiao C, Zhao Y, Li B, Liu Y, Peng Y, Yang X, Shi J, Gao X, Wang D. New insights into mechanisms of berberine in alleviating reproductive disorders of polycystic ovary syndrome: Anti-inflammatory properties. Eur J Pharmacol. 2023 Jan 15;939:175433.
Go to original source...
Go to PubMed...
- Xu Y, Qiao J. Association of insulin resistance and elevated androgen levels with polycystic ovarian syndrome (PCOS): A review of literature. J Healthc Eng. 2022 Mar 21;2022:9240569.
Go to original source...
Go to PubMed...
- Xue J, Li X, Liu P, Li K, Sha L, Yang X, Zhu L, Wang Z, Dong Y, Zhang L, Lei H, Zhang X, Dong X, Wang H. Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr J. 2019 Oct 28;66(10):859-70.
Go to original source...
Go to PubMed...
- Zare S, Nabiuni M, Tayanloo A, Hoseini S, Karimzadeh-Bardei L. The effects of Urtica dioica extract on lipid profile, insulin resistance index and liver histology in polycystic ovary syndrome-induced Wistar rats. Fut Nat Prod. 2015;1(2):23-33.
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