Antiatopic dermatitis activity of Lissachatina fulica mucin: Network pharmacology analysis and experimental validation.

Lissachatina fulica mucin (LFM) has been used as a nutraceutical, therapeutic agent, and cosmetic ingredient. The bioactivity of mucin depends on bioactive compounds whose composition is strongly influenced by the snail's diet. This study investigated the bioactive compounds in L. fulica mucin as potential therapeutic agents for atopic dermatitis (AD). LFM was collected from snails fed long beans and melon rinds for 4 weeks, freeze-dried, and analyzed using liquid chromatography-mass spectrometry followed by network pharmacology (NP) analysis to identify its bioactive compounds. A total of 60 BALB/c mice were sensitized on the dorsal skin with 1% 2,4-dinitrochlorobenzene and subsequently treated with dexamethasone or LFM cream (5% or 10%), which was applied daily for 7 days. Skin samples were collected on days 0, 3, 5, and 7 for immunohistological analysis. The results demonstrated that LFM contained 61 bioactive compounds, 16 of which interacted with seven target proteins: CCL2, TNF, PTGS2, SYK, MMP9, AKT1, and ICAM1. The NP analysis identified three major bioactive compounds in LFM-macamide, N-benzyloleamide, and a compound tentatively annotated as eplerenone-that potentially targeted CCL2 and TNF, which may serve as key regulators associated with the anti-AD effects of LFM. LFM 5% cream significantly reduced Atopic Dermatitis Severity Index (ADSI) scores and interleukin-1β (IL-1β) expression on day 5 (p < 0.05). LFM normalized epidermal thickness and increased the numbers of macrophages and mast cells (p < 0.05), suggesting a potential role in tissue remodeling and inflammation resolution during skin recovery. LFM demonstrated potential anti-AD effects by modulating CCL2- and TNF-associated pathways. LFM 5% cream reduced ADSI scores and IL-1β expression while normalizing epidermal thickness, potentially through immunomodulatory responses during the skin recovery phase.