Promising drug candidates for the treatment of polycystic ovary syndrome (PCOS) as alternatives to the classical medication metformin.

Autor: Anbar HS; Department of Clinical Pharmacy and Pharmacotherapeutics, Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates. Electronic address: dr.hanan@dpc.edu., Vahora NY; Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates., Shah HL; Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates., Azam MM; Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates., Islam T; Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates., Hersi F; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates., Omar HA; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt., Dohle W; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom., Potter BVL; Medicinal Chemistry & Drug Discovery, Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom., El-Gamal MI; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2023 Dec 05; Vol. 960, pp. 176119. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1016/j.ejphar.2023.176119
Abstrakt: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder that affects women of reproductive age. It is characterized by abnormal production of androgens, typically present in small quantities in females. This study aimed to investigate the therapeutic potential of Irosustat (STX64), STX140, and compound 1G as new drug candidates for the treatment of letrozole-induced PCOS in female Wistar rats. 36 rats were divided into six groups of equal size. PCOS was induced in all groups, except the normal control group, by administering letrozole orally (1 mg/kg/day for 35 days). The onset of abnormal estrous cycle was confirmed by examining daily vaginal smears under a microscope. Subsequently, each rat group was assigned to a different treatment regimen, including one control group, one letrozole group, one metformin group (500 mg/kg/day) as a reference drug, and the other groups received a different drug candidate orally for 30 days. After treatment, blood collection was performed for biochemical measurements and determination of oxidative stress markers. The rats were dissected to separate ovaries and uterus for morphological, histological, and western blotting studies. Treatment with the drug candidates improved the ovaries and uterus weight measurements compared to the untreated PCOS group. The three tested drug candidates demonstrated promising improvements in lipid profile, blood glucose level, testosterone, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels. In addition, western blotting confirmed their promising effects on Akt, mTOR, and AMPK-α pathways. This study led to the discovery of three promising drug candidates for the management of PCOS as alternatives to metformin.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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