What question did this study set out to answer?

Investigate the active compounds in four Epimedium species for their anti-hepatocellular carcinoma (HCC) properties.

April 25, 2026Journal of Hepatocellular Carcinoma0 citationsOpen Access

Pharmacodynamic Material Basis of the Components of Four Epimedium Species with Activities Against Hepatocellular Carcinoma Based on Biological Target Networks and Multi-Omics Analysis

XLXudong LiaoSichuan University JLJinzhong LiuDalian University of Technology ZPZhenyu PangEast China University of Technology

Key Points

Investigate the active compounds in four Epimedium species for their anti-hepatocellular carcinoma (HCC) properties.
Screened Epimedium extracts for anti-HCC activity using HepG2 cells
Utilized network pharmacology and HPLC to identify key compounds and targets
Conducted in vivo studies on H22 tumor-bearing mice to validate findings.
CMPLX significantly suppressed HCC proliferation in vitro and in vivo.
Mechanistically, CMPLX reduced expression of p-Akt, p-PI3K, and Bcl-2, promoting apoptosis.
Integrated analysis showed negative correlation between lignin/kaempferol derivatives and Escherichia coli abundance.

Abstract

Aim: Epimedium plants are used in traditional Chinese medicine due to their medicinal properties and can be clinically used for the treatment of liver cancer. Using network pharmacology and HPLC, we identified a key anti-HCC complex, CMPLX (containing icariin and kaempferol), from four Epimedium species. In vitro and in vivo studies demonstrated that CMPLX suppresses HCC proliferation by downregulating p-Akt, p-PI3K, and Bcl-2 expression. Untargeted metabolomics and gut microbiome analysis revealed significant negative correlations between serum levels of lignin/kaempferol derivatives and Escherichia coli abundance. These findings highlight CMPLX as a promising candidate for HCC drug development. Purpose: Investigate the pharmacodynamic material basis of the components of four Epimedium species with activities against hepatocellular carcinoma based on biological target networks and multi-omics analysis. Materials and Methods: We first screened four Epimedium extracts for anti-HCC activity using HepG2 cells. Shared bioactive compounds were identified through network pharmacology and HPLC, defining core target AKT1 and key complex CMPLX (icariin and kaempferol). Molecular docking/dynamics simulations confirmed CMPLX-AKT1 binding. In vitro assays (CCK-8, wound healing, colony formation, Annexin V/PI, Western blot) demonstrated CMPLX inhibits proliferation, migration, and induces apoptosis via PI3K/AKT/Bcl-2 pathway. In vivo validation in H22 tumor-bearing mice showed tumor suppression, corroborated by histology, serum metabolomics and gut microbiota analysis. Results: CMPLX suppressed hepatocellular carcinoma proliferation in vitro and in vivo. Mechanistically, it downregulated p-Akt, p-PI3K, and Bcl-2 expression, inhibiting growth and promoting apoptosis in HepG2 cells. Integrated multi-omics revealed CMPLX treatment elevated flavonoid/kaempferol derivatives while reducing EnterobacteriaceaeA/Escherichia abundance, with Marinifilaceae dominating the gut microbiota. Crucially, lignan/kaempferol derivatives showed significant negative correlation with Escherichia levels. Conclusion: CMPLX demonstrated synergistic anti-HCC efficacy in vitro and in vivo. Multi-omics analysis revealed its modulation of tumor-related pathways and gut microbiota composition, collectively contributing to tumor suppression. Keywords: Epimedium, hepatocellular carcinoma, metabolomics, gut microbiota

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