Study on serum metabolomics and network pharmacology of Cangfu Daotan decoction treating polycystic ovary syndrome in rats
Objective To investigate the effects of Cangfu Daotan decoction on serum endogenous markers in rats with polycystic ovary syndrome(PCOS)by ultra-performance liquid chromatography-tandem Q exactive quadrupole-electrostatic field orbitrap mass spectro-metry(UHPLC-QE-MS),and explore its role pathway based on the network pharmacology.Methods Forty rats were randomly divided into four groups:normal group,model group,Daying-35 group,and Cangfu Daotan group,with 10 rats in each group.The PCOS models were induced by letrozole.After successful induction,the rats in Daying-35 group received Daying-35 by gavage once a day for 28 d,while the rats in Cangfu Daotan group were administered Cangfu Daotan decoction by gavage once a day for 28 d.ELISA was used to measure the serum levels of follicle-stimulating growth hormone(FSH),luteinizing hormone(LH),testosterone(T),and estradiol(E2)in rats.Hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of ovary in rats.UHPLC-QE-MS was used to analyze the serum samples of rats in each group.The relevant differential metabolites were screened based on principal component analysis(PC A)and orthogonal partial least squares discriminant analysis(OPLS-DA).The related metabolic pathways were searched according to the MetaboAnalyst database.Network pharmacology was used to explore the key targets of Cangfu Daotan decoc-tion treating PCOS.KEGG database was utilized for pathway enrichment and analysis,and the"metabolite-reaction-enzyme-gene"network was constructed with the assistance of the MetScape.Results Compared with normal group,the serum FSH content was significantly increased in model group(P＜0.05),and the contents of LH,T,and E2 were also significantly increased(P＜0.01).Compared with model group,the serum contents of LH,T,and E2 were significantly reduced in Daying-35 group(P＜0.01),and the serum T level was significantly reduced(P＜0.05),and the contents of LH and E2 were also decreased in Cangfu Daotan group(P＜0.01).Compared with model group,the morphology of ovarian tissue in both Daying-35 group and Cangfu Daotan group were significantly improved.A total of 15 differential metabolites of Cangfu Daotan decoction treating polycystic ovary syndrome were identified by metabolomics,which were involved in pathways such as steroid hormone biosynthesis,glycerophospholipid metabolism,arginine and proline metabolism.Network pharmacological analysis revealed that the core targets of Cangfu Daotan decoction in treating PCOS included AKT1,ESR1,and EGFR.KEGG enrichment analysis indicated that the involved main pathways were endocrine resistance,steroid synthesis,and estrogen signaling pathway.The'metabolite-reaction-enzyme-gene'network was constructed using the MetScape to successfully identify six key targets:CYP1B1,CYP19A1,AKR1C1,AKR1C3,HSD17B1,and HSD17B2,which involved in the steroid hormone biosynthesis pathways.Conclusion Cangfu Daotan decoction has potential efficacy in treating PCOS rats,which may be related to its regulatory effects on the biosynthetic and metabolic pathways of steroid hormones.The endogenous markers for treat-ment,including 17α-hydroxypregnenolone,progesterone,and corticosterone,are useful to monitor the therapeutic outcomes.
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