Extracts of the leaves of Pyrus ussuriensis Maxim. Alleviate itch sensation via TSLP-dependent manner in mouse models of atopic dermatitis

Pyrus ussuriensis Maxim. commonly known as "Sandolbae" in Korean is a pear tree widely distributed across East Asia. Recent studies indicate that P. ussuriensis Maxim. leaves (PUL) have antipruritic effects. This study aimed to determine the effects of PUL extract and its fractions in decreasing the itch sensation and skin lesions in two distinct animal models of atopic dermatitis (AD) induced by dinitrofluorobenzene (DNFB) or house dust mite (HDM). Our results showed that the total ethanol extract of PUL decreased the scratching behavior in mice with DNFB- and HDM-induced AD. Moreover, the ethyl acetate fraction of PUL significantly improved the overall condition of the mice with AD induced by HDM. Further, we used HEK293T cells that express receptors and ion channels for thymic stromal lymphopoietin (TSLP), a potent pruritogen for AD, to determine the mechanisms underlying the antipruritic effects of PUL extract/fractions. Specific subfractions of the PUL strongly inhibited the increase in calcium levels induced by TSLP. In addition, the specific subfraction of PUL inhibited the TSLP-induced increase in calcium levels in cultured mouse dorsal root ganglia neurons. Thus, our results showed that the PUL extract could be effective for alleviating pruritus, and the antipruritic effects were exerted probably via the inhibition of the TSLP pathway in peripheral sensory neurons governing the itch sensation in AD.