Targeting the PI3K/AKT signaling pathway by Xihuang Pill to restrict osteosarcoma progression: an integrated network pharmacology and in vivo/vitro study.

Osteosarcoma (OS) is an aggressive bone malignancy with limited treatment options. Xihuang Pill (XHP), a traditional Chinese medicine formulation, has shown anti-tumour activity, but its mechanisms in OS remain unclear. This study integrated UPLC-QTOF-MS, network pharmacology, molecular docking, and experimental validation to identify the active components and therapeutic targets of XHP against OS. Network and survival analyses indicated that the PI3K/AKT pathway may be the key therapeutic axis. In vitro, XHP inhibited OS cell proliferation and migration, induced apoptosis, and caused cell cycle arrest in a dose- and time-dependent manner. In vivo, XHP suppressed xenograft tumour growth and improved physiological indicators in nude mice. RT-qPCR, Western blotting, and immunohistochemistry further confirmed that XHP exerted anti-OS effects by inhibiting PI3K/AKT signalling. These findings suggest that XHP may suppress OS progression through the PI3K/AKT pathway and has potential as a therapeutic candidate for OS.