Phytochemical Transformations of Panax notoginseng Saponins During Thermal Processing and Their Potential Implications for Iron Homeostasis Through Hepcidin-Related Pathways

Panax notoginseng has been used in Chinese materia medica for centuries, with the classical principle “sheng da shu bu” distinguishing raw roots used for acute hemostasis from thermally processed roots traditionally used for blood tonification. However, direct experimental evidence linking processing-induced phytochemical changes to hepcidin regulation remains lacking. This review examines how thermal processing of P. notoginseng may influence hepcidin-related pathways by integrating evidence from phytochemical transformation, hepatocyte signaling, and gut–liver axis biology. Thermal processing induces deglycosylation, dehydration, and isomerization of native saponins, generating rare, more lipophilic ginsenosides, including 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5. These products may have altered pharmacokinetic properties relative to their native precursors. Studies of isolated ginsenosides enriched during thermal processing in non-iron models provide indirect evidence for effects on upstream inflammatory or gut–liver pathways relevant to hepcidin induction. Microbial biotransformation of orally administered saponins may also modify intestinal barrier function and inflammatory context, but it is distinct from thermal processing. Whether a chemically characterized processed P. notoginseng preparation reduces hepatic HAMP expression or circulating hepcidin, preserves ferroportin abundance, or improves iron availability in vivo has not been established.