Morchella Polysaccharides in Oxidative Stress—Structure–Activity Relationships, Redox Signaling, and Translational Evidence

Morchella polysaccharides are commonly labeled as antioxidants because they quench radicals in chemical assays, yet this designation does not establish biological redox efficacy. This critical narrative review reframes these fungal polymers as candidate redox-modulating biomacromolecules. A structured search of PubMed and OpenAlex through 17 August 2026 yielded 84 unique records after deduplication; 31 core Morchella-polysaccharide reports with redox-relevant experimental evidence were mapped, supplemented by five mechanistically adjacent studies. Evidence was graded from chemical assays (E1) to human intervention (E5), with a separate causality score (M0–M2). Structure-resolved studies indicate that molecular weight, branching, charge, conformation, source, and acetylation or degradation can modify activity, but process-related co-variation and incomplete purity controls preclude universal structure–activity rules. Cellular and animal studies repeatedly implicate PI3K/Akt–Nrf2/HO-1, AMPK/Sirt1, mitochondrial apoptosis, NF-κB/NLRP3, and gut-mediated pathways, although most reported links remain associative. Within the databases and search strategy used, no eligible human intervention study was identified. We propose a translational roadmap requiring identity-controlled materials, orthogonal redox endpoints, causal pathway perturbation, exposure and microbiota studies, and standardized early-phase trials. The field should move beyond DPPH-positive claims toward reproducible mechanisms and biologically credible redox protection.