Effect of NAE on Polycystic Ovarian Syndrome (PCOS)

Summary

Polycystic Ovarian Syndrome (PCOS) is a multifaceted endocrine metabolic condition impacting about 5-10% of women throughout their reproductive lifespan. It is influenced by neuroendocrine dysfunction, insulin resistance, chronic low-grade inflammation, and ovarian oxidative stress. Existing medications, including metformin, clomiphene citrate, and anti-androgens, provide only limited advantages and are frequently restricted by side effects such as gastrointestinal intolerance, teratogenic risks, and weight gain. NAE (family Lamiaceae) is a fragrant perennial herb indigenous to the Himalayan and sub-Himalayan areas of Pakistan and Afghanistan. Phytochemical profiling of this plant has revealed high concentrations of flavonoids (luteolin, apigenin, quercetin), phenolic acids (rosmarinic and caffeic acid), terpenoids (nepetalactones), and glycosides. In a preclinical study lasting 30 days that involved Letrozole induced PCOS in Albino Wistar rats, the oral delivery of crude extract (350 and 500 mg/kg) and its methanol/butanol fractions (64 mg/kg; 12.5mg/kg) significantly restored estrous cyclicity, decreased serum LH and testosterone levels, normalized the LH/FSH ratio, enhanced insulin sensitivity (reduced HOMA IR), corrected dyslipidaemia, and reversed ovarian histopathological alterations. Molecular analysis by qRT PCR showed upregulation of IL 4 and downregulation of AR, CYP-17, TLR4, TNF α, and NF κB. Based on this multi targeted preclinical efficacy and a favourable safety profile, this clinical trial will assess the safety and effectiveness of a standardised NAE in women with PCOS, compared to metformin and combination therapy over 4 months.

Timeline

Start

2025-04-10

Primary completion

2026-05-30

Completion

2026-06-15

Publications

• Background Hosseini S, Shabani F, Nayebzadeh M, Asadi F, Kabiranaraki Y, Asadpour M, Golavar Y, Asadi S, Etezadi A. Neutrophils and NETosis in polycystic ovary syndrome: unraveling the immuno-metabolic thromboinflammatory axis. Eur J Med Res. 2026 Jan 27;31(1):331. doi: 10.1186/s40001-026-03927-7.
• Background Houston EJ, Templeman NM. Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS. J Endocrinol. 2025 Mar 12;265(2):e240269. doi: 10.1530/JOE-24-0269. Print 2025 May 1.
• Background Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside. Int J Mol Sci. 2023 Sep 15;24(18):14126. doi: 10.3390/ijms241814126.
• Background Zhao W, Li M, Jia C, Ali I, Chen L. Anti-inflammatory effect of a pimarane diterpenoid isolated from Nepeta adenophyta Hedge based on a network analysis approach and experimental assessment. Front Pharmacol. 2025 Dec 18;16:1652902. doi: 10.3389/fphar.2025.1652902. eCollection 2025.
• Background Dashti S, Ashouri A, Bahri N. Herbal compounds in the treatment of polycystic ovary syndrome: an updated systematic review. J Ovarian Res. 2026 Feb 27;19(1):132. doi: 10.1186/s13048-026-02030-z.
• Background Li C, Chen L, Zhao Y, Chen S, Fu L, Jiang Y, Gao S, Liu Z, Wang F, Zhu X, Rao J, Zhang J, Zhou X. Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model. Gene. 2017 Jan 20;598:20-26. doi: 10.1016/j.gene.2016.10.033. Epub 2016 Oct 21.
• Background Sharma A, Cooper R, Bhardwaj G, Cannoo DS. The genus Nepeta: Traditional uses, phytochemicals and pharmacological properties. J Ethnopharmacol. 2021 Mar 25;268:113679. doi: 10.1016/j.jep.2020.113679. Epub 2020 Dec 8.
• Background Wu X, Yi W, Liu X. Precision Targeted Therapy for PCOS: Emerging Drugs, Translational Challenges, and Future Opportunities. Biomedicines. 2026 Jan 19;14(1):213. doi: 10.3390/biomedicines14010213.
• Background Vakili S, Koohpeyma F, Samare-Najaf M, Namavar Jahromi B, Jafarinia M, Goharitaban S, Savardashtaki A, Samareh A, Amini F, Hashempur MH. Investigating the effects of rosmarinic acid on ovarian tissue, inflammatory markers, and sex hormones in polycystic ovary syndrome rats. Physiol Rep. 2025 Apr;13(7):e70304. doi: 10.14814/phy2.70304.
• Background Chen T, Jia F, Yu Y, Zhang W, Wang C, Zhu S, Zhang N, Liu X. Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review. Molecules. 2022 Jul 13;27(14):4476. doi: 10.3390/molecules27144476.
• Background Lonardo MS, Cacciapuoti N, Guida B, Di Lorenzo M, Chiurazzi M, Damiano S, Menale C. Hypothalamic-Ovarian axis and Adiposity Relationship in Polycystic Ovary Syndrome: Physiopathology and Therapeutic Options for the Management of Metabolic and Inflammatory Aspects. Curr Obes Rep. 2024 Mar;13(1):51-70. doi: 10.1007/s13679-023-00531-2. Epub 2024 Jan 3.
• Background Manouchehri A, Abbaszadeh S, Ahmadi M, Nejad FK, Bahmani M, Dastyar N. Polycystic ovaries and herbal remedies: A systematic review. JBRA Assist Reprod. 2023 Mar 30;27(1):85-91. doi: 10.5935/1518-0557.20220024.
• Background Ndefo UA, Eaton A, Green MR. Polycystic ovary syndrome: a review of treatment options with a focus on pharmacological approaches. P T. 2013 Jun;38(6):336-55.

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