Abstract
The root bark of Cudrania tricuspidata has been reported to have anti-sclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activities. In the present study, the effect of 16 compounds from C. tricuspidata on tumor necrosis factor-α+interferon-γ-treated HaCaT cells were investigated. Among these 16 compounds, 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds, namely, steppogenin (2), cudraflavone C (6), macluraxanthone B (12), 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3- methoxyxanthone (13), cudraflavanone B (4), and cudratricusxanthone L (14), were selected for further experiments. These six compounds decreased the expression levels of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activation-regulated chemokine (TARC), and downregulated the protein expression levels of intercellular adhesion molecule-1. Compounds 2, 6, 12, 4, and 14 inhibited nuclear factor-kappa B p65 translocation to the nucleus; however, compound 13 showed no significant effects. In addition, extracellular signal regulatory kinase-1/2 phosphorylation was only inhibited by compound 14, whereas p38 phosphorylation was inhibited by compounds 13 and 4. Taken together, the compounds from C. tricuspidata showed potential to be further developed as therapeutic agents to suppress inflammation in skin cells.
Highlights
Cudrania tricuspidata Bureau (Moraceae) is a tree that is found in China, Korea, and Japan
The stimulation of keratinocytes by tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) induces the expression of pro-inflammatory cytokines, such as IL-6 and IL-8
Compounds 6 and 14 were effective in inhibiting COX-2 and Intercellular adhesion molecule (ICAM)-1 expression. These results suggest that compounds 6 and 14 could inhibit chemokines and cytokines by inhibiting COX-2 and ICAM-1 expression in skin cells
Summary
Cudrania tricuspidata Bureau (Moraceae) is a tree that is found in China, Korea, and Japan. The root bark of C. tricuspidata has been reported to exhibit anti-sclerotic [6], neuroprotective [7], anti-inflammatory [8], mast cell activation [9], cytotoxic [10], pancreatic lipase inhibitory [11], and monoamine oxidase suppressive effects [12]. The stimulation of keratinocytes by tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) is highly dependent on their activation and this stimulation induces the expression and secretion of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activationregulated chemokine (TARC), which are regulated These factors contribute to the recruitment and infiltration of inflammatory cells in the skin [25]. The purpose of this study was to investigate the effects of 16 compounds from C. tricuspidata on skin inflammation
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