Process-Programmed Extraction–Structure–Activity Relationships (ESAR) in edible and medicinal mushroom polysaccharides: a mechanistic and application-oriented framework

To bridge these gaps, this review (2020-2025) applies an extraction-driven structure-activity relationship (ESAR) framework that directly links processing conditions to structural features, mechanisms, and functional outcomes. It prioritizes well-characterized β-glucans where defined structural features allow direct mapping from extraction parameters to molecular architecture and biological effects. The objective is to shift the field from "finding an active extract" to engineering process-defined polymer architectures that deliver targeted mechanisms and reproducible, application-specific outcomes. Key scientific concepts of the review: Within ESAR, extraction variables such as solvent system, temperature, pH, and enzymatic or physical assistance influence branching patterns, molecular-weight distributions, and conformational features such as triple-helix stability. These structural attributes in turn influence bioactivity by governing receptor engagement and activation pathways. Comparative analyses across representative β-glucans reveal that differences in molecular weight ranges, branching patterns, and helix/coil conformations account for the distinct potencies observed across studies. It also clarifies common sources of variability related to strain differences, cultivation substrate, processing severity, and analytical methods. This review introduces ESAR as a unifying framework that converts fragmented polysaccharide studies into predictive design principles for real-world translation. It demonstrates how extraction-defined molecular engineering can drive reproducible development of functional foods, nutraceuticals, and adjuvant therapeutics. Such reproducibility is essential for translating laboratory findings into reliable industrial and clinical applications.