UPLC-Q-TOF-MS/MS Profiling and Synergistic Anti-HCC Activity of Gallic Acid From Compound Muji Granules Combined With hUC-MSC-Exos.

Hepatocellular carcinoma (HCC) lacks effective therapies. Compound Muji Granules (MJ), a traditional Chinese medicine, shows potential anti-HCC activity, but its material basis and synergistic mechanism with exosomal delivery remain unclear. Using UPLC-Q-TOF-MS/MS, 98 compounds were identified in MJ, including 25 blood-absorbed and 23 tissue-distributed components, with gallic acid (GA) as the core active constituent. hUC-MSC-derived exosomes (hUC-MSCs-Exos) were prepared and combined with MJ or GA. In HepG2 cells and rat HCC organoids, exosome-combined treatment significantly reduced IC50, increased apoptosis and necrosis, and inhibited ATP production. Transcriptomic analysis and qPCR revealed regulation of the IL-17/MAPK/p53 axis, with downregulation of MEK1/2, CREB1, and IL17A, and activation of TP53. These findings indicate that MJ exerts anti-HCC efficacy through multi-component synergy, with GA as the main material basis, and hUC-MSCs-Exos enhance these effects by modulating IL-17/MAPK/p53 signaling, inhibiting tumor proliferation and energy metabolism, and promoting apoptosis.