ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
This article is part of the Research TopicPlant-Derived Bioactives in Disease Modulation: Bridging Molecular Mechanisms and Therapeutic ApplicationsView all 4 articles
Eriodictyol Alleviates Ovarian Dysfunction in a Mouse Model of Premature Ovarian Failure via the PI3K/Akt/NF-κB Pathway and Suppression of Macrophage Inflammation
Provisionally accepted
- 1Heilongjiang University of Chinese Medicine, Harbin, China
- 2Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Background: Premature ovarian failure (POF) is a significant cause of female infertility characterized by amenorrhea, hypergonadotropism, and hypoestrogenism, for which effective treatments are limited. Eriodictyol, a natural flavonoid, possesses potent anti-inflammatory properties, but its effects on POF remain unexplored. This study aimed to investigate the therapeutic potential of eriodictyol in a mouse model of chemotherapy-induced POF and to elucidate its underlying molecular mechanism. Methods: A POF model was established in C57BL/6 mice by cyclophosphamide injection. Mice were then treated with eriodictyol (20, 40, or 80 mg/kg) for 4 weeks. Ovarian function was evaluated by estrous cyclicity, ovarian index, and serum hormone levels. The mechanism was investigated using a combination of computational prediction and experimental validation, including in vivo Western blotting and an in vitro macrophage-granulosa cell co-culture system. Results: Eriodictyol treatment markedly restored estrous cyclicity, increased the ovarian index, decreased serum follicle-stimulating hormone (FSH), and elevated serum estradiol (E2) and anti-Müllerian hormone (AMH) levels in POF mice. To explore the mechanism, network analysis was first employed to predict potential targets, which identified the PI3K/Akt/NF-κB signaling pathway. This computational hypothesis was then experimentally validated; Western blot analysis confirmed that eriodictyol significantly inhibited the phosphorylation of PI3K, Akt, and NF-κB p65 in ovarian tissues. Furthermore, molecular docking suggested a strong binding affinity between eriodictyol and Akt. Corroborating these findings, in vitro experiments demonstrated that eriodictyol pre-treatment of macrophages protected co-cultured granulosa cells from inflammatory damage. Conclusions: Eriodictyol alleviates chemotherapy-induced ovarian dysfunction by inhibiting the PI3K/Akt/NF-κB inflammatory pathway and suppressing macrophage-mediated damage to granulosa cells. These findings identify eriodictyol as a promising therapeutic candidate for POF.
Keywords: premature ovarian failure, Eriodictyol, PI3K/Akt/NF-κB, Inflammation, macrophage, granulosa cell
Received: 22 Sep 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 qu, Liu, Wang, Sui, Zhang, Wu, Luo and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Min Sun, sunmin1975@hljucm.edu.cn
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