Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets for improving PCOS phenotypes by minocycline

Kian, Mahdie and Hosseini, Elham and Abdizadeh, Tooba and Yousef Langaee, Taimour and Khajouei, Azadeh and Ghasemi, Sorayya (2022) Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets for improving PCOS phenotypes by minocycline. EXCLI Journal, 21. pp. 400-414. ISSN 16112156

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Abstract

Polycystic ovary syndrome (PCOS) is the most common cause of women’s infertility. Some inflammatory pathways play a pivotal role in the pathogenesis of PCOS. This study aimed to investigate the possible beneficial effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a PCOS model. A molecular docking study was implemented using Molecular Operating Environment (MOE) software. The PCOS was induced in NMRI mice (mean body weight 14.47±0.23) by 28 days estradiol valerate injection (2 mg/kg/day). The mice were then divided into six groups (n=8 per group, mean body weight 17.77± 0.26): control (received normal saline), PCOS model, control for minocycline, minocycline treated PCOS (50 mg/kg), let-rozole treated PCOS (0.5 mg/kg), and metformin-treated PCOS (300 mg/kg). Serum FSH, LH, estradiol (E2), and testosterone were detected by ELISA. The ovarian tissues were stained by hematoxylin and eosin. The CMKLR1 and INSR expression levels were determined by Real-time-PCR. The molecular docking studies showed scores of-10.92 and-9.30 kcal/mol, respectively, for minocycline with CMKLR1 and INSR. Estradiol valerate treatment led to a significant increase in E2, graffian follicle, and decrease in corpus luteum (CL) num-bers (P<0.05), while minocycline treatment improved these PCOS features. The minocycline treatment signifi-cantly decreased the CMKLR1 expression and increased the INSR expression (P<0.05) while the CMKLR1 expression was increased in PCOS model. Minocycline may improve ovulation in PCOS model by returning E2 to a normal level and increasing CL number (ovulation signs). These beneficial outcomes may be related to the changes in CMKLR1 and INSR gene expression involved in glucose metabolism and inflammation.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: chemokine like receptor 1; chemokine receptor; estradiol; estradiol valerate; follitropin; insulin receptor; letrozole; luteinizing hormone; metformin; minocycline; testosterone; unclassified drug, animal experiment; animal model; animal tissue; Article; controlled study; corpus luteum; enzyme linked immunosorbent assay; estradiol blood level; female; follitropin blood level; glucose metabolism; inflammation; luteinizing hormone blood level; molecular docking; mouse; nonhuman; ovary follicle; ovary polycystic disease; ovary tissue; ovulation; phenotype; protein expression level; real time polymerase chain reaction; testosterone blood level
Subjects: WP Gynecology
WQ Obstetrics
QU Biochemistry > Cell biology and genetics
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: zeynab . bagheri
Date Deposited: 16 Mar 2022 05:03
Last Modified: 16 Mar 2022 05:03
URI: http://eprints.skums.ac.ir/id/eprint/9443

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