The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of Fraxinus rhynchophylla Hance Bark on Contact Dermatitis in Mice.

Abstract

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<-6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.