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Chrysin attenuates estradiol-induced endometrial hyperplasia in rats via enhancing PPARα activity

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Abstract

Endometrial hyperplasia (EH) is a complex condition that commonly affects women after menopause. Since the current available treatments for EH are mainly invasive, there is a need for developing new treatment modalities. Chrysin (Ch) is a dihydroxyflavone with numerous promising therapeutic potentials. In this study, Ch’s protective effects on estradiol (E2)-induced EH were studied in rats. Animals were allocated randomly to five groups and were treated for 4 weeks as follows: Group 1, control: received the vehicle; group 2, Ch: received Ch 25 mg/kg; group 3, estradiol (E2): received E2 (3 mg/kg) 3 × weekly subcutaneously and the vehicle. Group 4, E2 + Ch 10 mg/kg and group 5, E2 + Ch 25 mg/kg: Ch was given once daily at 10 mg/kg or 25 mg/kg, respectively. In addition, E2 was administered 3 × weekly (3 mg/kg) in groups 4 and 5. Ch inhibited the E2-induced increase in uterine weights and histopathological changes. Ch lowered the cyclin D1 expression. Ch raised the caspase-3 content and Bax mRNA expression. Furthermore, it corrected the raised Bcl2 mRNA expression due to E2. Ch inhibited MDA accumulation and GSH depletion. It also prevents E2-induced SOD and GPx exhaustion. It also ameliorated the rise in NFκB, TNF-α, and IL-6 expression. These effects were correlated with an enhanced PPARα activity ratio relative to the E2 group. This suggests that Ch attenuates EH in this model by exerting anti-proliferative, anti-oxidant, and anti-inflammatory effects partially through increasing PPARα activity.

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Acknowledgements

The author is grateful to Prof. Ashraf B. Abdel-Naim, Department of Pharmacology & Toxicology, King Abdulaziz University, Jeddah, Saudi Arabia, for his help in revising the manuscript.

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  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Basma Ghazi Eid

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Correspondence to Basma Ghazi Eid.

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All animal handling procedures were approved and supervised by the Research Ethics Committee, the Faculty of Pharmacy, King Abdulaziz University (Reference No: PH-1442–52).

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Eid, B.G. Chrysin attenuates estradiol-induced endometrial hyperplasia in rats via enhancing PPARα activity. Environ Sci Pollut Res 29, 54273–54281 (2022). https://doi.org/10.1007/s11356-022-19206-x

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