Evaluation of the therapeutic potential and underlying mechanisms of synephrine, a component of Kampo medicine, against allergic rhinitis

Abstract The mechanisms of action of Kampo medicines as treatments for allergic rhinitis are unknown. In this study, we aimed to identify novel potential therapeutic agents for allergic rhinitis and to elucidate their underlying mechanisms. Different components of Kampo medicines (crude drugs) were screened for their ability to inhibit the secretion of thymic stromal lymphopoietin (TSLP), a cytokine secreted during allergen exposure. Synephrine (SYN) exhibited the strongest inhibitory effect. In an early-phase allergic reaction, histidine decarboxylase (HDC) and its receptor are activated, leading to the secretion of TSLP. Mucins are thought to be produced as a late-phase reaction. We examined the action of SYN in cultures of human nasal epithelial cells both during mono-stimulation and co-stimulation with activating agents. Based on its inhibition of the histamine H1 receptor and HDC mRNA expression, SYN was assumed to reduce the histamine production. Increased expression of the HDC protein was confirmed in tissues of patients with allergic rhinitis via western blotting. In addition, SYN inhibited TSLP at the mRNA and protein levels and inhibited mucin 5AC mRNA expression. Its inhibitory effects on both early- and late-phase allergic reactions indicate that SYN can serve as a novel therapeutic agent with potential leukotriene antagonist-like activity.