Study of natto extract for the amelioration of dinitrochlorobenzene-induced atopic dermatitis by integrating untargeted metabolomics, network pharmacology, and molecular simulation

The health benefits of natto, a fermented soy product, have gained attention, but its effects on atopic dermatitis are not well-studied. This study aims to investigate the effects of natto extract on atopic dermatitis and to understand its underlying mechanisms. A mouse model of DNCB-induced atopic dermatitis was utilized to evaluate the intervention effects. Results showed that natto extract could significantly ameliorate the symptoms of atopic dermatitis, reduce the spleen index, attenuate dorsal skin lesions, and reduce the levels of IgE, IL-4, and IFN-γ in the serum. A total of 865 components were identified by UPLC-MS/MS-based untargeted metabolomics. Glycitein, hispidulin, and aurantiamide acetate were identified as key active components by network pharmacology. Interleukin-6, tumor necrosis factor, and prostaglandin endoperoxide synthase 2 were the core targets. Crucial signaling pathways involved Th17 cell differentiation, tumor necrosis factor signaling, and toll-like receptor signaling pathways. Molecular docking and dynamics simulation results demonstrated stable interactions between most active ingredients and core targets via hydrogen bond and hydrophobic interactions. These findings suggest that natto extract can ameliorate atopic dermatitis, enhance the understanding of the actions and mechanisms of its active ingredients, and provide a theoretical foundation for future research.