Inhibitory Effects and Potential Mechanism of Yokukansankachimpihange on SDS-induced Itch-associated Responses in Mice

Abstract

Yokukansankachimpihange (YKSCH) is a Chinese formula proven in Japan to be an effective treatment for pruritus in patients with atopic dermatitis or chronic urticaria and dry eczema with psychoneurotic symptoms, such as insomnia. Sodium dodecyl sulfate (SDS) may cause skin irritation in both humans and animals. Adverse effects, such as skin dryness, barrier destruction, dermatitis, and pruritus, developed following the repeated application of 10% SDS to a local site. Therefore, the present study investigated the antipruritic effects of YKSCH on skin irritation induced by a repeated SDS stimulation in mice and attempted to elucidate the underlying mechanism of action. ICR mice were stimulated with 10% SDS and co-treated with oral YKSCH extract for four days. Only oral YKSCH extract was administered on the fifth day. Scratching behavior was observed 24 h after the last application of SDS. Intraepidermal nerve growth was investigated by an immunofluorescence analysis. NGF concentrations in the epidermis were measured using an enzyme-linked immunosorbent assay. The expression of amphiregulin (Areg) and semaphorin 3A (Sema3A) was assessed by quantitative real-time PCR. The oral administration of YKSCH (200-400 mg/kg) dose-dependently suppressed pruritus, significantly reduced intraepidermal nerve growth, and down-regulated epidermal Areg mRNA expression in SDS-treated mice. These results suggest that YKSCH exerts antipruritic effects against SDS-induced pruritus in mice. The mechanism of action of YKSCH may involve reductions in intraepidermal nerve density due to the down-regulated expression of Areg.