Exploring the Therapeutic Potential of Marjoram (Origanum Majorana L.) in Polycystic Ovary Syndrome: Insights from Serum Metabolomics, Network Pharmacology and Experimental Validation

Overview

Journal BMC Complement Med Ther

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2025 Feb 21

PMID 39984989

Authors

Aliaa M Elfiky

Reham S Ibrahim

Amira R Khattab

Mai O Kadry

Naglaa M Ammar

Eman Shawky

Affiliations

Soon will be listed here.

Abstract

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with significant metabolic and hormonal dysregulation. Marjoram (Origanum majorana L.), known for its medicinal properties, has potential in managing PCOS through various bioactive compounds.

Objective: This study aims to evaluate the effects of marjoram on PCOS symptoms using serum pharmacochemistry, network pharmacology, and molecular docking in a DHEA-induced rat model.

Methods: Polycystic Ovary Syndrome (PCOS) was induced in rats using dehydroepiandrosterone (DHEA). Marjoram's therapeutic effects were evaluated by analyzing oxidative stress biomarkers, hormone levels, and ovarian histopathology. Untargeted serum metabolomics, conducted with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC TQD-MS/MS), identified key bioactive compounds. These compounds were then examined through network pharmacology to map their interactions with PCOS-related pathways, with findings validated via molecular docking.

Results: Marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose. Histopathological evaluation showed fewer ovarian cysts and improved follicular structure with marjoram administration. Network pharmacology analysis highlighted the steroid hormone biosynthesis and estrogen signaling pathways as critical targets, with apigenin and oleic acid identified as active compounds. Molecular docking confirmed strong interactions of these compounds with core PCOS-associated proteins, further supporting marjoram's potential in modulating PCOS symptoms.

Conclusion: This study reveals that marjoram contains a diverse range of active compounds that can modulate crucial biochemical and histological markers related to PCOS. By combining serum pharmacochemistry with network pharmacology, the research highlights marjoram's potential as a natural supplement to help alleviate PCOS symptoms and slow the syndrome's progression. These findings support further investigation into marjoram's role as a complementary therapy for managing PCOS.

References

Ammar N, Farag M, Kholeif T, Metwally N, M El-Sheikh N, El Gendy A . Serum metabolomics reveals the mechanistic role of functional foods and exercise for obesity management in rats. J Pharm Biomed Anal. 2017; 142:91-101. DOI: 10.1016/j.jpba.2017.05.001. View

Silvestrini A, Meucci E, Ricerca B, Mancini A . Total Antioxidant Capacity: Biochemical Aspects and Clinical Significance. Int J Mol Sci. 2023; 24(13). PMC: 10341416. DOI: 10.3390/ijms241310978. View

Peng F, Hu Y, Peng S, Zeng N, Shi L . Apigenin exerts protective effect and restores ovarian function in dehydroepiandrosterone induced polycystic ovary syndrome rats: a biochemical and histological analysis. Ann Med. 2022; 54(1):578-587. PMC: 8843206. DOI: 10.1080/07853890.2022.2034933. View

Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska A . Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int J Mol Sci. 2021; 22(7). PMC: 8038770. DOI: 10.3390/ijms22073789. View

Rao C, Zhou X, Lei Z . Functional luteinizing hormone/chorionic gonadotropin receptors in human adrenal cortical H295R cells. Biol Reprod. 2004; 71(2):579-87. DOI: 10.1095/biolreprod.104.027300. View

Mahana A, Hammoda H, Khalifa A, Elblehi S, Harraz F, Shawky E . Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of ground cherry (Physalis pruinosa L.) in treatment of type 2 diabetes mellitus in rats. J Ethnopharmacol. 2022; 300:115750. DOI: 10.1016/j.jep.2022.115750. View

Kanafchian M, Esmaeilzadeh S, Mahjoub S, Rahsepar M, Ghasemi M . Status of Serum Copper, Magnesium, and Total Antioxidant Capacity in Patients with Polycystic Ovary Syndrome. Biol Trace Elem Res. 2019; 193(1):111-117. DOI: 10.1007/s12011-019-01705-7. View

Liu S, Jia Y, Meng S, Luo Y, Yang Q, Pan Z . Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review. Int J Mol Sci. 2023; 24(11). PMC: 10252376. DOI: 10.3390/ijms24119205. View

Hossain M, Camphuis G, Aguilo-Aguayo I, Gangopadhyay N, Rai D . Antioxidant activity guided separation of major polyphenols of marjoram (Origanum majorana L.) using flash chromatography and their identification by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Sep Sci. 2014; 37(22):3205-13. DOI: 10.1002/jssc.201400597. View

10.

Archibong A, Rideout M, Harris K, Ramesh A . OXIDATIVE STRESS IN REPRODUCTIVE TOXICOLOGY. Curr Opin Toxicol. 2018; 7:95-101. PMC: 6086129. DOI: 10.1016/j.cotox.2017.10.004. View

11.

Kadry M . Liposomal glutathione as a promising candidate for immunological rheumatoid arthritis therapy. Heliyon. 2019; 5(7):e02162. PMC: 6661417. DOI: 10.1016/j.heliyon.2019.e02162. View

12.

Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R . Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016; 106(1):6-15. DOI: 10.1016/j.fertnstert.2016.05.003. View

13.

Rudnicka E, Duszewska A, Kucharski M, Tyczynski P, Smolarczyk R . OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress in polycystic ovary syndrome. Reproduction. 2022; 164(6):F145-F154. DOI: 10.1530/REP-22-0152. View

14.

Chiang Y, Lin I, Huang K, Chen H, Ali M, Huang Y . Caffeic acid's role in mitigating polycystic ovary syndrome by countering apoptosis and ER stress triggered by oxidative stress. Biomed Pharmacother. 2023; 166:115327. DOI: 10.1016/j.biopha.2023.115327. View

15.

Baskol G, Aygen E, Erdem F, Caniklioglu A, Narin F, Sahin Y . Assessment of paraoxonase 1, xanthine oxidase and glutathione peroxidase activities, nitric oxide and thiol levels in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2011; 91(3):326-30. DOI: 10.1111/j.1600-0412.2011.01337.x. View

16.

Basheer M, Bhat A, Hajam Y, El-Saber Batiha G, Ataya F, Fouad D . Melatonin as a promising therapeutic intervention for restoring ovarian function in letrozole-induced polycystic ovary syndrome rats. Heliyon. 2023; 9(11):e21237. PMC: 10643099. DOI: 10.1016/j.heliyon.2023.e21237. View

17.

Liu H, Zheng A, Liu H, Yu H, Wu X, Xiao C . Identification of three novel polyphenolic compounds, origanine A-C, with unique skeleton from Origanum vulgare L. using the hyphenated LC-DAD-SPE-NMR/MS methods. J Agric Food Chem. 2011; 60(1):129-35. DOI: 10.1021/jf204406u. View

18.

Cui N, Yang Y, Xu Y, Zhang J, Jiang L, Hao G . Decreased expression of fatty acid amide hydrolase in women with polycystic ovary syndrome. Gynecol Endocrinol. 2017; 33(5):368-372. DOI: 10.1080/09513590.2016.1269742. View

19.

Kafali H, Iriadam M, Ozardali I, Demir N . Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res. 2004; 35(2):103-8. DOI: 10.1016/j.arcmed.2003.10.005. View

20.

Musso C, Shawker T, Cochran E, Javor E, Young J, Gorden P . Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth. Clin Endocrinol (Oxf). 2005; 63(1):73-8. DOI: 10.1111/j.1365-2265.2005.02302.x. View