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Integrated Metabolomics, Network Pharmacology, and Molecular Dynamics Simulations Reveal the Potential Anti-Melanoma Mechanisms of Inonotus hispidus
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DOI：10.3390/cimb48080814.png)
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Abstract
En 中文
Melanoma is a highly aggressive malignancy characterized by pronounced metastatic potential, marked heterogeneity, and complex therapeutic resistance. Although immunotherapy and targeted therapy have improved the prognosis of some patients, their long-term clinical application remains constrained by limited therapeutic responses, drug resistance, and adverse effects. In this study, widely targeted metabolomics, network pharmacology, molecular docking, and molecular dynamics simulations were integrated to systematically investigate the potential mechanisms underlying the anti-melanoma effects of Inonotus hispidus SH-18. Fruiting bodies of Sang Huang at the Juvenile, Growth, and Maturation stages were analyzed using UPLC-MS/MS, identifying 1575 metabolites across 13 chemical classes. PCA explained 67.91% of the total variance (PC1, 43.54%; PC2, 24.37%), while the OPLS-DA models yielded Q2 values of 0.964, 0.966, and 0.981 for IH-G vs. IH-J, IH-M vs. IH-G, and IH-M vs. IH-J, respectively. A total of 1099 differentially accumulated metabolites were identified, including 304 (140 up-accumulated and 164 down-accumulated), 311 (195 up-accumulated and 116 down-accumulated), and 484 (278 up-accumulated and 206 down-accumulated) in the three respective comparisons. Based on the experimentally detected metabolites, network pharmacology and bioinformatics analyses suggested that the active constituents of Sang Huang may synergistically suppress melanoma cell proliferation, survival, immune evasion, angiogenesis, invasion, and metastasis by regulating multiple pathways and signaling axes, including the TP53-p21 axis. Molecular docking showed that the candidate active compounds exhibited binding potential with core targets, among which ursolic acid displayed favorable binding capacity toward all core targets. Molecular dynamics simulations further supported the stability of these interactions. Notably, ursolic acid was most abundant in samples from the Juvenile stage, suggesting that this stage may be preferred for ursolic acid enrichment and subsequent activity evaluation. These findings suggest the potential therapeutic value of Sang Huang in melanoma treatment.
Keywords:
Sang Huang
melanoma
targeted metabolomics
network pharmacology
molecular dynamics simulation
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1.9K
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