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Exploring the mechanism of esculetin extracted from Chroogomphus rutilus in treating liver cancer based on network pharmacology, molecular docking, and in vivo experimental validation

Year: 2025
Type: article
Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Chroogomphus rutilus (C. rutilus) is a traditional Chinese medicine recorded in the book Illustrations of Medicinal Fungi in China that possesses a long history of use for the treatment of various diseases, including cancer. Esculetin (ES), the primary pharmacologically active ingredient of C. rutilus, exerts significant therapeutic effects against liver cancer (LC). Nonetheless, the underlying therapeutic mechanisms of ES against LC remain poorly understood. AIM OF THE STUDY: To investigate the mechanisms of ES in LC treatment. MATERIALS AND METHODS: ES was isolated and identified from C. rutilus. Subsequently, related targets and mechanism of ES against LC were predicted through network pharmacology and molecular docking. The antitumor effect of ES was examined using H22 tumor-bearing mouse models. The antitumor mechanism of ES was elucidated and validated using TUNEL, enzyme-linked immunosorbent assay (ELISA), immunofluorescence analysis, Western blot (WB), and quantitative real-time polymerase chain reaction (qPCR). RESULTS: The chemical structure was determined using NMR carbon and hydrogen spectra. Network pharmacology analysis indicated that ES exerted anti-LC effects via the PI3K/AKT signaling pathway and associated proteins. TUNEL and ELISA revealed that ES exhibited an obvious antitumor effect in vivo and that the levels of TNF-α, IFN-γ, IL-2, and IL-6 were significantly increased. Immunofluorescence, WB, and qPCR analyses showed that ES upregulated the protein expression of Bax, caspase-3, and caspase-9 and downregulated the protein expression of Bcl-2, VEGF, and p-AKT. CONCLUSION: This study demonstrates that the mechanisms of ES in LC treatment include enhancing immunity, inhibiting angiogenesis, and promoting apoptosis of tumor cells.
DOI: 10.1016/j.jep.2025.119837
Authors: Shuang Jiang, Haiying Bao
Language: English
Open Access status: hybrid
Estimated APC paid: $3,740
OpenAlex ID: W4409577160
FWCI: 3.829
Cites: 69
Cited by: 8
Related to: 10