Pharmacological investigation of vitamin E with combined oral contraceptives on INHBA gene against PCOS that intricate through melatonin PKC pathway

Abstract

The most prevalent endocrine and metabolic condition in women of reproductive age are polycystic ovary syndrome (PCOS) with significant risk factors such as circadian rhythm and melatonin disruption. The aim of this study is to assess the effect of vitamin E in combination with a combined oral contraceptive (COC) on continuous light-induced PCOS using hormonal measures, oxidative stress (OS) indicators, and the inhibin beta-A (INHBA) gene, which targets the melatonin protein kinase C (PKC) pathway. An in silico technique anticipated INHBA's binding affinity for vitamin E and COC. For the in vivo investigation (IAEC/240/2021), female SD rats were divided into six groups and subjected to a 16-week induction period, followed by a 2-month test drug treatment with drospirenone (DRSP) as a standard. Serum testosterone, FSH, melatonin, and OS were calculated as hormonal markers. The expression of the INHBA gene was studied to see if it could be linked to the circadian rhythm and OS via the melatonin PKC pathway. According to the in silico study, vitamin E and DRSP had higher binding energy for the INHBA (–8.6 kcal/mol and –8.4 kcal/mol, respectively). When compared to the control group, in vivo results showed a substantial decrease in testosterone levels (p = .05), as well as changes in FSH (p = .78) and melatonin (p = .13). IHNBA gene expression has also dramatically increased, stimulating FSH production in the pituitary gland. Vitamin E and COC concomitantly are beneficial against PCOS because it modulates OS, which in turn influences circadian rhythm and the melatonin PKC pathway.

Keywords:

• Polycystic ovarian syndrome
• vitamin E
• drospirenone
• melatonin
• protein kinase C
• inhibin beta-A

Ethics approval

This study was approved by Institutional Animal Ethics Committee (IAEC), SRM College of Pharmacy, SRM Institute of Science and Technology, India (IAEC/240/2021). All the procedures were carried out as per the CPCSEA and ARRIVE 2.0 guidelines.

Acknowledgments

We thank SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, India for their support in this research work.

Disclosure statement

The authors report no conflict of interest.

Authors’ contributions

Conceived and designed the experiment: RFB; performed the experiment: RFB, SM; analyzed the data, wrote the manuscript: RFB; final edit of the paper: SM.

Additional information

Funding

There was no funding received for this study.