Exploring the effect of Gouqi Nuzhen Liuhe decoction on the PI3K/mTOR signaling pathway for premature ovarian insufficiency based on system pharmacology

Abstract

Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

Keywords

• Gouqi Nuzhen Liuhe decoction
• Premature ovarian insufficiency
• System pharmacology
• PI3K/mTOR signaling