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Insights into Vitamin E with Combined Oral Contraceptive on INSR Gene in PCOS by Integrating In Silico and In Vivo Approaches

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Abstract

Polycystic ovarian syndrome (PCOS) is a hormone disorder common among reproductive-aged women. This is associated with the symptoms like an irregular menstrual cycle, excess androgens, and polycystic ovary. Interestingly, vitamin E acts like the hormone progesterone and improves insulin sensitivity in PCOS. The study aims to evaluate the therapeutic effect of vitamin E in combination with combined oral contraceptive (COC) against PCOS by in silico and in vivo methods. The therapeutic effect of vitamin E (25 and 50mg/kg) in combination with COC (0.4mg/kg) was screened by the in silico method using Auto dock vina 4.2.6. Additionally, in vivo studies with a letrozole-induced PCOS model were performed in 30 female SD rats (n = 6 in each group) for 8 weeks with different doses of vitamin E. Furthermore, histopathological features and the insulin receptor (INSR) gene were scrutinized. An in silico study showed that drospirenone and vitamin E have an excellent affinity to bind to INSR and have higher binding energy (− 8.5 kcal/mol and − 8.7 kcal/mol, respectively). In vivo results showed a significant reduction in elevated testosterone levels compared to that of the PCOS group; follicle-stimulating hormone (FSH) and insulin levels also showed significant changes and reversed anti-oxidant levels in a dose-dependent manner. Ovarian histopathological changes were observed in different follicle counts in addition to the INSR gene, which showed changes in densitometry values. Supplementation of vitamin E combined with COC could be effective against PCOS, and clinical studies must be carried out further.

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Acknowledgements

We express our thanks and gratitude to the supervisors and professors of SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India, who supported this work.

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All authors contributed to the study conception and design. Rukaiah Fatma Begum: conceptualization, methodology, investigation, formal analysis. Writing- original draft preparation. Sumithra M: methodology, supervision, and writing—review and editing.

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Correspondence to Sumithra Mohan.

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This study was performed in line with the principles of the CPCSEA guidelines and approval from the Institutional Animal Ethical Committee, SRM College of Pharmacy, SRMIST, Kattankulathur. IAEC number: IAEC/240/2021.

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Begum, R.F., Mohan, S. Insights into Vitamin E with Combined Oral Contraceptive on INSR Gene in PCOS by Integrating In Silico and In Vivo Approaches. Appl Biochem Biotechnol (2023). https://doi.org/10.1007/s12010-023-04710-8

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