1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose: A Comprehensive Review of Its Biological Actions and Anti-Cancer Effects

The natural compound 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG) is a hydrolyzable gallotannin abundantly found in numerous medicinal plants and widely recognized for its diverse pharmacological properties. This comprehensive review examines the biological actions of PGG with particular emphasis on its anti-cancer mechanisms. PGG exerts its anti-neoplastic effects through multiple molecular pathways, including direct protein targeting, modulation of key signaling cascades such as PI3K/AKT and MAPK, induction of apoptosis, and cell cycle arrest. Recent evidence has identified HER2 as a direct molecular target of PGG in colorectal cancer, while other studies have demonstrated its efficacy against gastric cancer, multiple myeloma, and various other malignancies. Beyond its anti-cancer properties, PGG exhibits significant anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Despite its therapeutic promise, the clinical translation of PGG is hampered by poor oral bioavailability due to chemical instability under alkaline conditions, enzymatic degradation, and limited intestinal permeability. This review synthesizes current knowledge regarding PGG's mechanisms of action, pharmacokinetic limitations, and therapeutic potential, while identifying critical areas for future research to facilitate its development as a clinical candidate.