Quercetin as the core constituent of Huanglian decoction: Targeting AKT1 for colorectal cancer therapy

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal carcinoma. Huanglian decoction (HD) has been applied to treat gastrointestinal disorders for millennia. Objectives: This study utilized network pharmacology strategies to establish the drug–compound–disease target network. Methods: To explore the biological functions and pathways involved, GO and KEGG enrichment analyses were conducted. To identify core targets from the findings, a protein-protein interaction (PPI) network was constructed. We utilized the molecular docking assay, CETSA and DARTS to validate the compound-target complex. The biological effects of the key compound on CRC cells were studied using CCK-8 assay, colony-formation assay, scratch test and trans well invasion assay. Results: Our findings indicated that half of the HD potential targets were CRC-related genes. PPI analysis identified 7 key genes: AKT1, ESR1, JUN, IL6, MYC, FOS and CCND1. Quercetin was identified as a core active compound of HD, which likely exerts its effects by targeting AKT1 and inhibiting the AKT-mTOR pathway, thereby suppressing the proliferation, migration and invasion of CRC cell lines (Caco-2 and SW480). Conclusion: The results suggest that HD has potential therapeutic properties against CRC. Its active ingredient, quercetin, exerted anti-CRC effects by binding to AKT1 and inhibiting the activation of the AKT-mTOR pathway.