Panax ginseng as a proteome-metabolome medicinal ecosystem: Reframing pharmacology beyond a strictly saponin-centric...

The pharmacological understanding of Panax ginseng has traditionally focused on ginsenosides (saponins) as the principal bioactive determinants for its anti-inflammatory, metabolic, and anticancer effects. However, advances in multi-omics, high-resolution proteomics, spatial metabolomics, and microbiome analysis are expanding this view beyond a metabolite-exclusive framework. Emerging evidence shows that the ginseng proteome undergoes dynamic remodeling in response to ecological stress, development, and processing, generating glycosylated proteoforms, stress-responsive proteins, and peptide derivatives with biological relevance. Concurrently, microbiome-mediated biotransformation reshapes metabolite bioactivity and immune-metabolic homeostasis. These observations support the consideration of P. ginseng as an expanded, multi-layered system built on the established saponin-centered architecture. While saponins remain the primary signaling axis, the peptide tier, including small proteins, may exert complementary influences through redox buffering, receptor-proximal modulation, and localized stress-response mechanisms. These distinct molecular tiers are thought to converge on shared regulatory hubs, such as nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), nuclear factor erythroid 2-related factor 2 (Nrf2), inflammasome signaling, and mitochondrial stress pathways. Although some catalytic stress mechanisms need experimental validation, structural and proteomic findings suggest that additional regulatory layers beyond classical signaling modulation merit systematic study. Modern technologies like data-independent acquisition proteomics, peptidomics, spatial omics, and AI-assisted network modeling now enable comprehensive interrogation of this cross-tier structure. Integrating proteomic, metabolomic, and microbiome axes is essential to refine mechanistic understanding, improve multidimensional standardization, and expand translational exploration in botanical pharmacology.