Mechanistic insights of Sargassum polycystum fatty oil compounds in cutaneous melanoma: in vitro, metabolomics guided-network pharmacology, molecular docking and dynamics approach

• S. polycystum HOE is rich in lipid compounds • S. polycystum HOE has anti-oxidant and anti-cutaneous melanoma properties • The anti-cutaneous melanoma compound was predicted to be a sterol compound • Dormatinone had a high binding affinity towards PTPN11 • S. polycystum HOE is involved in oncogenic signaling and immune regulation Cutaneous melanoma remains a global health issue. While lipid-rich oils have long been used in Traditional Chinese Medicine (TCM) for cancer therapy, brown macroalgae Sargassum also provide lipid derivative compounds with therapeutic potential, including in the modulation of skin diseases. However, the molecular mechanisms of fatty oil compounds from Sargassum species, such as Sargassum polycystum , in relation to cutaneous melanoma remain unexplored. UHPLC-HRMS-based untargeted metabolomics was performed to identify the compounds in Sargassum polycystum hexane oil extract (HOE). Identified compounds were then subjected to computational analysis, including network pharmacology analysis, followed by molecular docking (Autodock Vina), molecular dynamics (GROMACS), and GO/KEGG enrichment analysis (DAVID and KEGG mapper). Finally, in vitro anti-oxidant analysis using DPPH assay and B16-F10 melanoma cytotoxic analysis using Resazurin assay were also performed. Untargeted metabolomics identified 62 drug-like compounds predicted to interact with cutaneous melanoma-related targets. Computational analysis identified Dormatinone, a sterol with strong affinity for PTPN11, an essential oncogenic gene and immune regulator in cutaneous melanoma. Enrichment analysis revealed the role of Sargassum polycystum HOE compounds in oncogenic signaling and immune regulation, while in vitro assays confirmed the extract’s anti-oxidant (IC 50 = 0.847 ± 0.02mg/mL) and B16-F10 melanoma cytotoxic activity (IC 50 = 0.481 ± 0.0014mg/mL). These findings indicate the potential of Sargassum polycystum HOE as a sterol-rich extract with anti-cutaneous melanoma activity, providing a basis for further drug development.