To Explore the Active Components, Targets, and Potential Effects of Emodin in the Treatment of Colorectal Cancer Based on Network Pharmacology

TL;DR

This study explores how emodin, a natural compound, fights colorectal cancer by identifying its key targets and mechanisms using network pharmacology and experiments.

Contribution

The study identifies emodin's multitarget, multipathway mechanism in colorectal cancer, particularly through the PPARγ–TP53 signaling axis.

Findings

Emodin significantly suppresses CRC cell proliferation and induces apoptosis in vitro.

In vivo experiments show emodin inhibits tumor growth and activates the PPARγ–TP53 signaling axis.

Key targets include CASP3, MMP9, BCL2, PTGS2, and IL1B, involved in apoptosis and inflammation.

Abstract

The objective was to investigate the effects and potential molecular mechanisms of emodin on colorectal cancer via network pharmacology combined with experimental validation.

The active components and targets of emodin were retrieved from TCMSP and BATMAN-TCM databases, while colorectal cancer (CRC)-related genes were screened via GeneCards, OMIM, and DisGeNET. The intersection targets were used to construct a compound–disease network and a protein–protein interaction (PPI) network. GO and KEGG enrichment analyses were conducted to reveal key biological functions and pathways. Molecular docking was used to assess binding affinities between core targets and active components. In vitro experiments (CCK-8, colony formation, and apoptosis assays) and in vivo xenograft models were performed to validate the antitumor effect of emodin. Quantitative real-time PCR and Western blot were used to evaluate the regulation of hub genes and signaling pathways.

A total of 37 active components and 235 targets of emodin were identified, of which 82 overlapped with CRC-related genes. Core targets (CASP3, MMP9, BCL2, PTGS2, and IL1B) were highlighted through network analysis. These targets were enriched in oxidative stress, apoptosis, inflammation, and metabolic pathways. Molecular docking showed strong interactions between emodin and hub targets. Emodin significantly suppressed proliferation, colony formation, and induced apoptosis in CRC cell lines in a dose-dependent manner. In vivo, emodin inhibited tumor growth and activated the PPARγ–TP53 signaling axis.

Emodin exerts anti-CRC effects via a multitarget, multipathway mechanism, particularly through modulation of the PPARγ–TP53 axis. These findings support emodin's potential as a natural compound for CRC treatment.

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