Morus alba fruits attenuates atopic dermatitis symptoms and pathology in vivo and in vitro via the regulation of barrier function, immune response and pruritus

Morus alba fruits (MAF) belong to the Moraceae family, which are known to be effective in treating diabetic, autoimmune, and hormonal diseases owing to its low toxicity. MAF, as excerpted from Donguibogam, a representative Korean medical encyclopedia protected by UNESCO, has been widely used to treat lumbago, arthritis, and diabetes. Based on these effects, MAF is investigated for unidentified effects of atopic dermatitis, characterized by complex etiology of skin barrier dysfunction, inflammation, and chronic pruritus.The antioxidant, inflammatory, and immunomodulatory properties of MAF and its bioactive compounds have been widely reported. According to an examination of 1-chloro-2,4-dinitrobenzene-induced AD-like skin lesions in NC/Nga mice, AD symptoms, such as increased dermatitis score, scratching frequency, immunoglobulin E, trans-epidermal water loss, epidermal thickness, and infiltration of mast cells, were relieved by topical MAF administration. They effectively attenuated cytokines and chemokines, such as interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, IL-17A, IL-22, IL-1β, tumor necrosis factor-α, thymic stromal lymphopoietin (TSLP), thymic- and activation-regulated chemokine, normal T cell expression, and macrophage-derived chemokine secretion at the mRNA level in TNF-α/IFN-γ induced HaCaT (human immortalized keratinocyte) cells.Both in vivo and in vitro models, MAF increased the expression of filaggrin, involucrin, and loricrin, as well as inhibited the activation of Janus kinase 2, signal transducer and activator of transcription proteins 1, and mitogen-activated protein kinase pathways, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38. Moreover, MAF reduced the expression of TSLP and periostin, which play important roles in skin pruritus as chronic pruritogenic factors.These data indicate that MAF could be used as a potential treatment for AD-like skin lesions by regulating the inflammatory response, improving physical skin barriers, and relieving symptomatic pruritus.