An alkaloid mixture, Cepharanthin®, suppresses the inflammatory response of T-lymphocytes and epithelial cells in an in vitro oral lichen planus model

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease for which an apparent cause has not been identified. OLP is refractory to treatment, and malignant transformation has been reported. Therefore, discovering drugs for OLP with few adverse effects over long-term administration is crucial. In this study, we established an in vitro OLP model to investigate the effects of Cepharanthin®, an alkaloid mixture derived from Stephania cephalantha Hayata, and its major four components on inflammation-related gene expression in epithelial cells and lymphocytes. Four alkaloids from Cepharanthin® suppressed expression of cytokine genes to various degrees in activated T cells, but the effect of Cepharanthin® as a drug formulation was limited. However, the four alkaloids and Cepharanthin® suppressed expression of cytokine genes in human oral epithelial cells when stimulated with IL-1β. In the OLP model, activated T cells increased inflammatory gene expression in epithelial cells, while Cepharanthin® suppressed this expression. An anti-inflammatory effect of Cepharanthin® was also observed by protein dot blot. These findings suggest that the effects of Cepharanthin® might occur in two ways: mild suppression of inflammatory cytokines production in T lymphocytes and strong suppression of the response of epithelial cells to inflammatory stimuli. The anti-inflammatory effects of Cepharanthin® on activated T cells and oral mucosal epithelial cells shown in this study support its potential clinical efficacy for OLP. Furthermore, the in vitro model established in this study could be used as a tool for examining the mechanisms of OLP pathogenesis and disease persistence.