Bioinformatics Reveals Mechanism of Zuoguiwan in Treating Polycystic Ovary Syndrome
10.13422/j.cnki.syfjx.20240906
- VernacularTitle:基于生物信息学技术探讨左归丸治疗多囊卵巢综合征的机制
- Author:
Jinrong ZHANG
1
;
Haotian LI
1
;
Hongming HUANG
1
;
Ali DENG
2
;
Min ZHAO
1
Author Information
1. School of Basic Medical Sciences，Hubei University of Chinese Medicine，Wuhan 430065，China
2. Affiliated Hospital of Hubei University of Chinese Medicine，Wuhan 430000，China
- Publication Type:Journal Article
- Keywords:
Zuoguiwan;
polycystic ovary syndrome;
network pharmacology;
metabolomics;
steroid hormone biosynthesis pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(17):77-86
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the potential mechanism of Zuoguiwan in ameliorating polycystic ovary syndrome （PCOS） by network pharmacology and liquid chromatography-mass spectrometry （LC-MS）-based metabolomics. MethodThe active ingredients and potential targets of Zuoguiwan for treating PCOS were predicted by bioinformatics. SD rats were assigned into a control group and a modeling group. The rat model of PCOS was established by gavage with letrozole （1 mg·kg-1） combined with feeding with a high-fat diet. At the end of modeling， the modeled rats were assigned into model （normal saline）， metformin （300 mg·kg-1）， and Zuoguiwan （concentrate 1.62 g·kg-1） groups. The body weight and oestrous cycle of each rat were recorded， and the ovary was stained with hematoxylin and eosin for observation of ovarian morphology. Enzyme-linked immunosorbent assay was employed to determine the serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-mullerian hormone （AMH）， testosterone （T）， and estradiol （E2）， and the LH/FSH ratio was calculated. Serum metabolomics of rats was conducted by orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen the metabolite-enriched pathways. Furthermore， network pharmacology and association analysis were employed construct the compound-response-enzyme-gene network. ResultA total of 503 potential targets of Zuoguiwan and 5 843 targets of PCOS were screened out， with 271 common targets. The Gene Ontology enrichment analysis revealed that the common targets were involved in the response to lipopolysaccharide， etc.， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment yielded 119 pathways. Animal experiments showed that compared with the control group， the model group presented increased body weight （P<0.01）， elevated LH and AMH levels （P<0.01）， increased LH/FSH ratio （P<0.01）， lowered E2 level （P<0.01）， and increased cystic follicles. Compared with the model group， Zuoguiwan and metformin decreased the body weight （P<0.01）， reduced atretic follicles and cystic follicles， increased mature follicles and corpus luteum， and thickened the granulosa layer. Moreover， Zuoguiwan lowered the T， FSH， LH， and AMH， and LH/FSH levels （P<0.01） and elevated the E2 level （P<0.01）. The principal component analysis and OPLS-DA in metabolomics showed that the differential metabolites between Zuoguiwan and model groups included 26 up-regulated metabolites in the Zuoguiwan group. There were 8 common pathways predicted by the KEGG enrichment analysis in network pharmacology and the metabolite enrichment in metabolomics. The results of topological analysis revealed the pathways of steroid hormone biosynthesis and glycerol-phospholipid metabolism， and the constructed compound-response-enzyme-gene network revealed that the key targets were protein kinase B1 （Akt1）， epithelial growth factor receptor （EGFR）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and mitogen-activated protein kinase 1 （MAPK1）. ConclusionZuoguiwan regulated the steroid hormone biosynthesis pathway to recover hormone levels， promote follicle production and development， and improve ovarian function， which may be the potential mechanism of this medicine in treating PCOS.
