Mechanism of Yishen Quzhuo Formula in Treating PCOS-IR Based on Network Pharmacology and Animal Experiments

doi:10.12280/gjszjk.20250141

Abstract

Abstract:

Objective: To investigate the mechanism of Yishen Quzhuo Formula in treating polycystic ovary syndrome with insulin resistance (PCOS-IR) through the network pharmacology and experimental validation. Methods: Active components and targets of Yishen Quzhuo Formula were retrieved from databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP). The targets of PCOS-IR-related disease were screened using GeneCards, OMIM, and DrugBank databases. A drug-component-target network was then constructed. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using STRING and DAVID. Molecular docking was conducted with AutodockTools 1.5.7 software. A PCOS-IR rat model was established using the high-fat diet combined with letrozole. Serum hormone levels and glucose metabolism indices were evaluated. The expression of key targets was validated via Western blotting and quantitative polymerase chain reaction (qPCR). Results: A total of 136 potential active components of Yishen Quzhuo Formula and 406 PCOS-IR-related targets were identified. Five core components, including kaempferol, quercetin, and β-sitosterol, were selected. The top 10 key targets, such as interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), protein kinase B1 (AKT1), heat shock protein 90 (HSP90), and tumor protein 53 (TP53), were ranked by the degree values in the core network, enriched in the pathways like advanced glycation end product-receptor for advanced glycation end product (AGE-RAGE) and phosphoinositide 3-kinase (PI3K)-AKT. Animal experiments showed that Yishen Quzhuo Formula significantly reduced the levels of serum luteinizing hormone (LH), testosterone, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) in PCOS-IR rats (all P<0.05), and downregulated the expressions of STAT3, epidermal growth factor receptor (EGFR) and HSP90 in the ovarian tissues of PCOS-IR rats, while upregulated the expressions of AKT1 and TP53 (all P<0.05). Conclusions: Yishen Quzhuo Formula ameliorates the endocrine abnormalities and glucose metabolism disorders of PCOS-IR through multi-component, multi-target and multi-pathway mechanisms.

Key words: Polycystic ovary syndrome, Insulin resistance, Pharmacology, Molecular docking simulation, Yishen Quzhuo formula, Network pharmacology

LI Meng-yuan, GAO Zheng, XU Xin. Mechanism of Yishen Quzhuo Formula in Treating PCOS-IR Based on Network Pharmacology and Animal Experiments[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(5): 353-360.

Figures/Tables 13

References 23

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基因	引物	序列（5′→3′）
GAPDH	正向	TCATTGACCTCAACTACATGG
	反向	TCGCTCCTGGAAGATGGTG
STAT3	正向	TTAACATTCTGGGCACGAACA
	反向	TGACAATCAAGGAGGCATCAC
AKT1	正向	CGACGTAGCCATTGTGAAGGAG
	反向	ATTGTGCCACTGAGAAGTTGTTG
TP53	正向	ATGGAGGATTCACAGTCGGATAT
	反向	CGCTGTGGTGGGCAGAATAT
EGFR	正向	CTCAGCAGGCCACACTTGTA
	反向	TGCATGGTTACTCCAGCTTAGA
HSP90	正向	ACATGCTGCGGAGGGTTAAG
	反向	CTGCTCGGAGTCATCTGTGGT

基因	引物	序列（5′→3′）
GAPDH	正向	TCATTGACCTCAACTACATGG
	反向	TCGCTCCTGGAAGATGGTG
STAT3	正向	TTAACATTCTGGGCACGAACA
	反向	TGACAATCAAGGAGGCATCAC
AKT1	正向	CGACGTAGCCATTGTGAAGGAG
	反向	ATTGTGCCACTGAGAAGTTGTTG
TP53	正向	ATGGAGGATTCACAGTCGGATAT
	反向	CGCTGTGGTGGGCAGAATAT
EGFR	正向	CTCAGCAGGCCACACTTGTA
	反向	TGCATGGTTACTCCAGCTTAGA
HSP90	正向	ACATGCTGCGGAGGGTTAAG
	反向	CTGCTCGGAGTCATCTGTGGT

编号	核心靶点	PDB ID	化合物	结合能（kcal/mol）
1	AKT1	8uw9	β-谷甾醇	-7.6
2	TP53	6vrn	山柰酚	-7.8
3	STAT3	6TLC	槲皮素	-8.6
4	EGFR	7zyn	7-甲氧基-2-甲基异黄酮	-6.4
5	HSP90	7s8y	木犀草素	-8.6

编号	核心靶点	PDB ID	化合物	结合能（kcal/mol）
1	AKT1	8uw9	β-谷甾醇	-7.6
2	TP53	6vrn	山柰酚	-7.8
3	STAT3	6TLC	槲皮素	-8.6
4	EGFR	7zyn	7-甲氧基-2-甲基异黄酮	-6.4
5	HSP90	7s8y	木犀草素	-8.6

组别	n	FSH （mIU/mL）	LH （mIU/mL）	LH/FSH 比值	睾酮（ng/mL）
空白组	8	1.766±0.317	7.438±0.374*	4.376±1.062*	0.643±0.032*
模型组	8	1.901±0.281	11.700±1.036	6.305±1.305	0.888±0.086
益肾祛浊方组	8	1.668±0.230	9.254±0.465*	5.656±0.918	0.763±0.086*
二甲双胍组	8	1.723±0.139	9.343±0.563*	5.456±0.582	0.758±0.068*
F		1.264	55.910	5.122	15.690
P		0.306	<0.001	0.006	<0.001