Anti-inflammatory potential of Lentinula edodes DMRO-356: Ethnopharmacological validation and multi-target molecular docking.

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ETHNOPHARMACOLOGICAL RELEVANCE: Lentinula edodes (shiitake) has long been used in East Asian medicine to reduce inflammation, boost vitality, and support immune function. Its therapeutic effects arise from the synergistic activity of multiple bioactive compounds, consistent with the ethnopharmacological preference for whole-extract remedies.

AIM OF THE STUDY: This study evaluated and compared the anti-inflammatory potential of L. edodes strains DMRO-34 and DMRO-356 through in vivo and in silico approaches, correlating pharmacological outcomes with HPLC-based phytochemical profiles.

MATERIALS AND METHODS: Ethanolic extracts (80 %) of both strains were tested in a carrageenan-induced rat paw edema model. Phytochemical profiling quantified phenolics, flavonoids, β-glucans, ergosterol, and ergothioneine. Molecular docking, 50 ns molecular dynamics (MD) simulations, binding energy analysis, ADMET predictions, and network pharmacology were employed to elucidate mechanisms and multi-target interactions.

RESULTS: DMRO-356 showed the highest paw edema inhibition (22.4 %) and contained elevated levels of β-glucans (30.37 %), ergosterol (2.85 ± 0.07 mg/g), and ergothioneine (1.42 ± 0.05 mg/g). Docking revealed strong interactions of ergosterol with TNF-α (-8.7 kcal/mol) and β-glucans with COX-2 (-8.3 kcal/mol). MD simulations confirmed stable ligand-protein complexes with high hydrogen bond occupancy (85.6 % and 78.2 %). Network pharmacology indicated modulation of NF-κB, MAPK, and JAK/STAT pathways.

CONCLUSIONS: L. edodes strain DMRO-356 demonstrates superior anti-inflammatory activity, driven by its enriched bioactive composition and stable multi-target interactions. These findings validate its traditional use and support its development as a safe, multi-target natural therapeutic for inflammation management.