Abstract

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.

Highlights

  • Introduction distributed under the terms andNelumbinis plumula is the green embryo of the mature seeds of Nelumbo nucifera Gaertn.The earliest documented record of Nelumbinis plumula is in the “Food Nature MateriaMedica” from the late Tang Dynasty [1]

  • We examined the role of neferine in TNF-α/IFN-γ-treated HaCaT cells to investigate whether neferine is a promising agent for the treatment of atopic dermatitis

  • Our results show that TNF-α and IFN-γ stimulate human keratinocytes to induce the expression of large amounts of inflammatory factors (IL-1β, IL-6, IL-8, TSLP, TARC, MDC, and RANTES)

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Summary

Introduction

Introduction distributed under the terms andNelumbinis plumula is the green embryo of the mature seeds of Nelumbo nucifera Gaertn.The earliest documented record of Nelumbinis plumula is in the “Food Nature MateriaMedica” from the late Tang Dynasty [1]. The earliest documented record of Nelumbinis plumula is in the “Food Nature Materia. Medica” from the late Tang Dynasty [1]. The “Compendium of Materia Medica” of the Ming. Dynasty records Nelumbinis plumula as “bitter, cold, non-toxic”. Medicine or as a health tea application, it has been proven that Nelumbinis plumula does have unique effects. According to Pharmacopoeia, dried Nelumbinis plumula contains no less than. The current alkaloid content is used as a standard for the quality evaluation of Nelumbinis plumula [1]. According to previous research reports, the main alkaloids in Nelumbinis plumula are liensinine, isoliensinine, and neferine, among which the content of neferine is the highest. Recent studies have demonstrated that neferine effectively prevents

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