Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Jun 2:14:1159657.
doi: 10.3389/fendo.2023.1159657. eCollection 2023.

The therapeutic role and potential mechanism of EGCG in obesity-related precocious puberty as determined by integrated metabolomics and network pharmacology

Qiuyun Gu  1 , Lina Xia  1 , Qiuju Du  1 , Ying Shao  1 , Jieyi He  1 , Peiying Wu  1 , Lingwei Liang  1 , Xiuhua Shen  2   3
Affiliations
Randomized Controlled Trial

The therapeutic role and potential mechanism of EGCG in obesity-related precocious puberty as determined by integrated metabolomics and network pharmacology

Qiuyun Gu et al. Front Endocrinol (Lausanne). .

Abstract

Objective: (-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study was to integrate metabolomics and network pharmacology to reveal the mechanism of EGCG in the prevention of obesity-related precocious puberty.

Materials and methods: A high-performance liquid chromatography-electrospray ionization ion-trap tandem mass spectrometry (LC-ESI-MS/MS) was used to analyze the impact of EGCG on serum metabolomics and associated metabolic pathways in a randomized controlled trial. Twelve weeks of EGCG capsules were given to obese girls in this trail. Additionally, the targets and pathways of EGCG in preventing obesity-related precocious puberty network pharmacology were predicted using network pharmacology. Finally, the mechanism of EGCG prevention of obesity-related precocious puberty was elucidated through integrated metabolomics and network pharmacology.

Results: Serum metabolomics screened 234 endogenous differential metabolites, and network pharmacology identified a total of 153 common targets. These metabolites and targets mainly enrichment pathways involving endocrine-related pathways (estrogen signaling pathway, insulin resistance, and insulin secretion), and signal transduction (PI3K-Akt, MAPK, and Jak-STAT signaling pathways). The integrated metabolomics and network pharmacology indicated that AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 may be key targets for EGCG in preventing obesity-related precocious puberty.

Conclusion: EGCG may contribute to preventing obesity-related precocious puberty through targets such as AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 and multiple signaling pathways, including the estrogen, PI3K-Akt, MAPK, and Jak-STAT pathways. This study provided a theoretical foundation for future research.

Keywords: EGCG; metabolomics; network pharmacology; obesity; precocious puberty.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Multivariate statistical analysis of metabolite profiles in serum in obese girls OPLS-DA score plots of the EGCG group and Placebo group in positive mode (A) and negative mode (B). (C) Heatmap of top 30 endogenous differential metabolites between two groups, *P < 0.05, **P < 0.01, ***P < 0.001. (D) KEGG signaling pathway enrichment analysis (P < 0.05). (E) Categories of endogenous differential metabolites.
Figure 2
Figure 2
An analysis of potential therapeutic targets based on a Venn diagram and a PPI network (A) Venn diagram of the common targets of EGCG, obesity and precocious puberty. (B) Potential therapeutic targets in the PPI network. (C) The bar plot of the protein–protein interaction network.
Figure 3
Figure 3
Gene Ontology (GO) enrichment analysis (A) GO enrichment analysis. The top 10 evidently enriched terms in each category. BP, biological process; CC, cellular component; MF, molecular function. (B) The top 10 enriched BP terms.
Figure 4
Figure 4
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway results (A) Statistical chart of the B-level classification of each pathway. (B) The top 20 significant pathways. Bubble size from large to small indicates the count of potential targets enriched in the pathway in descending order. Bubble color from red to green indicates the -log (p value) in descending order. (C) The top 20 significantly enriched differential pathway circle maps.
Figure 5
Figure 5
Potential therapeutic targets based on evidently enriched pathways The green nodes represent potential therapeutic targets of EGCG obesity and precocious puberty in PI3K-AKT pathway (A) and estrogen pathway (B). (C) EGCG-target-pathway multiple interactive network.
Figure 6
Figure 6
Molecular docking analysis (A) EGCG with AKT1. (B) EGCG with EGFR. (C) EGCG with ESR1. (D) EGCG with IGF1. (E) EGCG with MAPK1. (F) EGCG with STAT3.
See this image and copyright information in PMC

References

    1. Bradley SH, Lawrence N, Steele C, Mohamed Z. Precocious puberty. BMJ (2020) 368:l6597. doi: 10.1136/bmj.l6597 - DOI - PubMed
    1. Gu Q, Luo Y, Ye J, Shen X. comparative efficacy and safety of three current clinical treatments for girls with central precocious puberty: a network meta-analysis. Endocr Pract (2019) 25:717–28. doi: 10.4158/EP-2019-0008 - DOI - PubMed
    1. Wu Y, Gu Q, Cui X, Zhu Z, Zang J, Wang Z, et al. . Higher poultry consumption was associated with an earlier age at menarche. Acta Paediatr (2021) 110:889–95. doi: 10.1111/apa.15554 - DOI - PubMed
    1. Chen M, Eugster EA. Central precocious puberty: update on diagnosis and treatment. Paediatr Drugs (2015) 17:273–81. doi: 10.1007/s40272-015-0130-8 - DOI - PMC - PubMed
    1. De Sanctis V, Soliman AT, Di Maio S, Soliman N, Elsedfy H. Long-term effects and significant adverse drug reactions (ADRs) associated with the use of gonadotropin-releasing hormone analogs (GnRHa) for central precocious puberty: a brief review of literature. Acta BioMed (2019) 90:345–59. doi: 10.23750/abm.v90i3.8736 - DOI - PMC - PubMed

Publication types