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Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2‐Foxo1‐GSH‐NF‐κB pathway.

Authors :
Jin, Shan
Wang, Yu‐Si
Huang, Ji‐Cheng
Wang, Ting‐Ting
Li, Bai‐Yu
Guo, Bin
Yue, Zhan‐Peng
Source :
Cell Biology International. Aug2024, Vol. 48 Issue 8, p1111-1123. 13p.
Publication Year :
2024

Abstract

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro‐inflammatory cytokine interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF‐κB) subunit p65 by DHEA and weakened the transcriptional activity of NF‐κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF‐κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2‐Foxo1‐GSH‐NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10656995
Volume :
48
Issue :
8
Database :
Academic Search Index
Journal :
Cell Biology International
Publication Type :
Academic Journal
Accession number :
178441635
Full Text :
https://doi.org/10.1002/cbin.12170