Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity

IntroductionEvidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn’s therapeutic targets and pathways in Western diet (WD)-induced obesity usi...

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Main Authors: Yu Liao, Mingchao Wang, Fuli Qin, Taotao Liu, Jiemei Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1571480/full
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author Yu Liao
Mingchao Wang
Fuli Qin
Taotao Liu
Jiemei Chen
author_facet Yu Liao
Mingchao Wang
Fuli Qin
Taotao Liu
Jiemei Chen
author_sort Yu Liao
collection DOAJ
description IntroductionEvidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn’s therapeutic targets and pathways in Western diet (WD)-induced obesity using integrated network pharmacology, transcriptomics, and experimental validation.MethodsA Western diet (WD)-induced mice model was used to evaluate the effectiveness of Cpn in ameliorating obesity. A network pharmacology analysis was then employed to identify the potential anti-obesity targets of Cpn. GO functional enrichment and KEGG pathway analysis were performed to elucidate the potential functions of the identified targets, followed by constructing a protein-protein interaction network to screen the core targets. Meanwhile, quantitative transcriptomics was conducted to validate and broaden the network pharmacology findings. Finally, molecular docking and quantitative real-time PCR assay were used for the core target validation.ResultsCpn treatment effectively alleviated obesity-related symptoms in WD-induced mice. The metabolic pathway, insulin signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, lipid and atherosclerosis pathway, and core targets including CPS1, HRAS, MAPK14, PAH, ALDOB, AKT1, GSK3B, HSP90AA1, BHMT2, EGFR, CASP3, MAT1A, APOM, APOA2, APOC3, and APOA1 are involved in regulating the therapeutic effect of Cpn.ConclusionThis study comprehensively uncovers the potential mechanism of Cpn against obesity based on network pharmacology and quantitative transcriptomics, which provides evidence for revealing the pathogenesis of obesity, suggesting that Cpn is a possible lead compound for anti-obesity treatment.
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spelling doaj-art-013b3666aabd4154b75bb221046d541e2025-08-20T03:49:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15714801571480Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesityYu Liao0Mingchao Wang1Fuli Qin2Taotao Liu3Jiemei Chen4Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaIntroductionEvidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn’s therapeutic targets and pathways in Western diet (WD)-induced obesity using integrated network pharmacology, transcriptomics, and experimental validation.MethodsA Western diet (WD)-induced mice model was used to evaluate the effectiveness of Cpn in ameliorating obesity. A network pharmacology analysis was then employed to identify the potential anti-obesity targets of Cpn. GO functional enrichment and KEGG pathway analysis were performed to elucidate the potential functions of the identified targets, followed by constructing a protein-protein interaction network to screen the core targets. Meanwhile, quantitative transcriptomics was conducted to validate and broaden the network pharmacology findings. Finally, molecular docking and quantitative real-time PCR assay were used for the core target validation.ResultsCpn treatment effectively alleviated obesity-related symptoms in WD-induced mice. The metabolic pathway, insulin signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, lipid and atherosclerosis pathway, and core targets including CPS1, HRAS, MAPK14, PAH, ALDOB, AKT1, GSK3B, HSP90AA1, BHMT2, EGFR, CASP3, MAT1A, APOM, APOA2, APOC3, and APOA1 are involved in regulating the therapeutic effect of Cpn.ConclusionThis study comprehensively uncovers the potential mechanism of Cpn against obesity based on network pharmacology and quantitative transcriptomics, which provides evidence for revealing the pathogenesis of obesity, suggesting that Cpn is a possible lead compound for anti-obesity treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1571480/fullcordycepinobesitynetwork pharmacologyquantitative transcriptomicsmolecular dockingexperimental validation
spellingShingle Yu Liao
Mingchao Wang
Fuli Qin
Taotao Liu
Jiemei Chen
Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
Frontiers in Pharmacology
cordycepin
obesity
network pharmacology
quantitative transcriptomics
molecular docking
experimental validation
title Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
title_full Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
title_fullStr Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
title_full_unstemmed Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
title_short Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
title_sort integrating network pharmacology quantitative transcriptomic analysis and experimental validation revealed the mechanism of cordycepin in the treatment of obesity
topic cordycepin
obesity
network pharmacology
quantitative transcriptomics
molecular docking
experimental validation
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1571480/full
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