Yulin Hukun Decoction Ameliorates Diminished Ovarian Reserve via PI3K/Akt/mTOR-Mediated Autophagy
10.13422/j.cnki.syfjx.20250139
- VernacularTitle:基于PI3K/Akt/mTOR介导的自噬探讨毓麟护坤汤改善卵巢储备功能下降机制
- Author:
Ruixia WANG
1
;
Huan CHENG
2
;
Yaxing FAN
2
;
Tingyun CAI
2
;
Meifang LI
1
Author Information
1. Shanxi Traditional Chinese Medicine Hospital， Taiyuan 030000， China
2. Shanxi University of Chinese Medicine， Jinzhong 030600， China
- Publication Type:Journal Article
- Keywords:
diminished ovarian reserve;
autophagy;
phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway;
Yulin Hukun decoction
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(18):77-85
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of Yulin Hukun decoction on autophagy mediated by phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in the mouse model of cyclophosphamide-induced diminished ovarian reserve and explore the follicular development-improving mechanism of this decoction. MethodsSixty female ICR mice with normal estrous cycle were assigned into a blank group （n=10） and a modeling group （n=50）. The model was established by intraperitoneal injection of cyclophosphamide （60 mg·kg-1） for 5 days. The successfully modeled mice were randomly grouped as follows： model， estradiol （0.26 mg·kg-1）， and high-， medium-， and low-dose （56.42， 28.21， 14.105 g·kg-1， respectively） Yulin Hukun decoction， with 10 mice in each group. The blank group and the model group received normal saline （10 mL·kg-1）. The intervention was performed once a day for 21 days. The general conditions， estrous cycle， body weight， and ovary index were observed and recorded for each group. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， and anti-Müllerian hormone （AMH） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the ovarian tissue were observed by hematoxylin-eosin staining. Western blot was employed to determine the protein levels of PI3K， Akt， mTOR， autophagy-related protein 7 （Atg7）， beclin1， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， ubiquitin-binding adaptor protein （p62）， forkhead box protein O1 （FoxO1）， and acetylated forkhead box protein O1 （Ac-FoxO1） in mouse ovaries. Real-time PCR was adopted to determine the mRNA levels of PI3K， Akt， mTOR， Atg7， beclin1， and LC3Ⅱ in the mouse ovarian tissue. ResultsCompared with the blank group， the model group had disturbed estrous cycle， decreased body weight （P<0.05）， loose ovarian structure with increased atretic follicles， increased serum FSH level （P<0.05）， and decreased AMH and estradiol levels （P<0.05）. Compared with the model group， the treatment groups showed recovered estrous cycles and body weight. The estradiol group and high- and medium-dose Yulin Hukun decoction groups showed declined FSH level （P<0.05） and elevated AMH levels （P<0.05）. In addition， the treatment groups showed downregulated protein levels of Atg7， LC3Ⅱ， beclin1， FoxO1， and Ac-FoxO1 （P<0.01）， upregulated protein levels of PI3K， Akt， mTOR， and p62 （P<0.01） in the ovarian tissue， gradual repair of the ovarian structure， with more intact and numerous follicles of various stages. ConclusionYulin Hukun decoction can inhibit autophagy in ovarian granulosa cells by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the expression of autophagy-related proteins and transcription factors， thereby improving follicular development and ovarian reserve.
