Network Pharmacology, Molecular Docking, and Experimental Validation on Guiluoshi Anzang Decoction Against Premature Ovarian Insufficiency

Yuanyuan Wu; Yunxia Long; Guangheng Su; Xiangping Fan; Guozhen He; Zhijuan Luo; Songping Luo

doi:10.2174/0113862073291139240506114446

Network Pharmacology, Molecular Docking, and Experimental Validation on Guiluoshi Anzang Decoction Against Premature Ovarian Insufficiency

Comb Chem High Throughput Screen. 2024 May 16. doi: 10.2174/0113862073291139240506114446. Online ahead of print.

Authors

Yuanyuan Wu^{1

2}, Yunxia Long³, Guangheng Su³, Xiangping Fan³, Guozhen He⁴, Zhijuan Luo¹, Songping Luo⁵

Affiliations

¹ Ruikang Affiliated Hospital of Guangxi Medical University Gynecology Nanning, China.
² First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou City, 510405, China.
³ Graduate School, Guangxi University of Chinese Medicine, Guangxi Province, Nanning City, 530000, China.
⁴ Guangxi University of Chinese Medicine School of Basic Medicine Nanning, China.
⁵ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou City, 510405, China.

PMID: 38757315
DOI: 10.2174/0113862073291139240506114446

Abstract

Background and objectives: Premature Ovarian Insufficiency (POI) is a disease suffered by women under the age of 40 when ovarian function has declined, seriously affecting both the physical and mental health of women. Guiluoshi Anzang decoction (GLSAZD) has been used for a long time and has a unique therapeutic effect on improving ovarian function. This study aims to investigate the mechanism of GLSAZD in treating POI through network pharmacology, molecular docking, and experimental verification.

Methods: In this study, the active ingredients of Guiluoshi Anzang Decoction and the targets of POI were obtained from TCMSP, BATMANN-TCM, Uniprot, GeneCards, and other databases, and network pharmacology analysis was performed. Molecular docking was conducted to validate the affinity of the main active ingredient of GLSAZD to key POI targets. A POI SD rat model was established, and HE staining, ELISA, Real-time PCR, and Western blot experiments were performed to verify the predicted core targets and the therapeutic effects.

Results: 10 core targets and the top 5 ingredients were screened out. Molecular docking showed core targets AKT1, CASP3, TNF, TP53, and IL6 had stable binding with the core 5 ingredients quercetin, kaempferol, beta-sitosterol, luteolin, and Stigmasterol. GO and KEGG enrichment analysis demonstrated the mechanism involved in the positive regulation of gene expression, PI3K-AKT signaling pathway, and apoptosis signaling pathways. Animal experiments indicated GLSAZD could up-regulate the protein expression of p-PI3K and p-AKT1 and the mRNA expression of STAT3 and VEGF, down-regulate TP53 and Cleaved Caspase-3 protein expression in rat`s ovarian tissues and serum TNF-α and IL-6 protein levels, activate PI3K-AKT signaling pathway and inhibit the apoptosis signaling pathway.

Conclusion: GLSAZD treats POI through multi-component, multi-target, and multi-pathway approaches. This study provided evidence for its clinical application in treating POI and shed light on the study of traditional medicine of the Guangxi Zhuang Autonomous Region in China.

Keywords: Apoptosis signaling pathway; Experimental verification.; Guiluoshi Anzang Decoction; Molecular docking; Network pharmacology; PI3K/AKT signaling pathway.