Unraveling the Antimelanogenic Potential of Poria cocos : Component Characterization, Spatial Distribution, and Inhibitory Mechanisms

Phytochemical investigation of the edible fungus Poria cocos (Poria cum Radix Pini, PRP) led to the isolation and identification of 40 lanostane-type triterpenoids (LTDs), including seven new LTDs. Six LTDs (2, 5, 14, 17, 23, 36) exhibited antimelanogenic activity in B16F10 cells and zebrafish. Structure–activity relationship analysis revealed that an α-oriented hydroxyl at C-3, absence of C-16 hydroxyl, and free C-3 hydroxyl are critical for high activity. LTD 14 suppressed melanogenesis by inhibiting the ERK pathway, downregulating MITF and tyrosinase. Molecular docking and dynamics predicted stable binding to tyrosinase, which was confirmed by SPR (KD = 148 nM). Additionally, MALDI-MSI was employed for the first time to spatially map the distribution of bioactive triterpenoids directly in P. cocos tissue, revealing that whitening-active LTDs 14, 17, and 23 are widely distributed across different anatomical parts. This study establishes an integrated paradigm from structural discovery to spatial mapping for edible bioresource development.