Shin Jae Young, Kim Bo Mi, Jang Seon Il
Institute of Health and Science, Jeonju University, Jeonju, Jeonbuk 55069, Republic of Korea.
Department of Chemical Engineering, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea.
Exp Ther Med. 2025 Apr 16;29(6):121. doi: 10.3892/etm.2025.12871. eCollection 2025 Jun.
Pruritus is a distressing symptom associated with various dermatological, systemic and neurological conditions, markedly impairing quality of life. Pruritus arises through histamine-dependent and histamine-independent pathways, involving mediators such as histamine, gastrin-releasing peptide (GRP), interleukin-31 (IL-31) and STAT3 signaling. The present study aimed to investigate the antipruritic effects of leaf extract (DLE) and its major constituent, myricitrin (MC), on ICR mice using compound 48/80 (histamine-dependent) and chloroquine (histamine-independent) itch models. Serum levels of histamine and IL-31 were measured by ELISA, and mast cell infiltration was assessed via toluidine blue staining. Furthermore, the expression and activation of GRP receptor (GRPR), IL-31RA and STAT3 in the spinal cord were analyzed using western blotting and immunofluorescence staining. Notably, DLE and MC significantly reduced scratching behavior, serum histamine levels and mast cell infiltration in both models. Immunofluorescence staining and western blot analysis revealed that DLE and MC downregulated GRPR, IL-31 receptor A and phosphorylated STAT3 expression in the spinal cord, indicating modulation of central itch signaling. Additionally, DLE and MC suppressed IL-31 levels in serum and skin tissues. These findings indicated that DLE and MC may alleviate pruritus through multiple mechanisms, including mast cell stabilization, histamine reduction and modulation of central itch pathways. The broad-spectrum antipruritic activity of DLE and MC highlights their potential as natural therapeutic agents for diverse pruritic conditions, offering a safer alternative to synthetic antipruritic drugs. Further research is warranted to validate these findings in clinical settings and to elucidate the molecular mechanisms underlying their efficacy.
瘙痒是一种令人苦恼的症状，与多种皮肤病、全身性疾病和神经系统疾病相关，会显著损害生活质量。瘙痒通过组胺依赖性和组胺非依赖性途径产生，涉及组胺、胃泌素释放肽（GRP）、白细胞介素-31（IL-31）和信号转导及转录激活因子3（STAT3）信号等介质。本研究旨在使用化合物48/80（组胺依赖性）和氯喹（组胺非依赖性）瘙痒模型，研究叶提取物（DLE）及其主要成分杨梅苷（MC）对ICR小鼠的止痒作用。通过酶联免疫吸附测定（ELISA）测量血清组胺和IL-31水平，并通过甲苯胺蓝染色评估肥大细胞浸润情况。此外，使用蛋白质免疫印迹法和免疫荧光染色分析脊髓中GRP受体（GRPR）、IL-31受体A（IL-31RA）和STAT3的表达及激活情况。值得注意的是，在两种模型中，DLE和MC均显著减少了搔抓行为、血清组胺水平和肥大细胞浸润。免疫荧光染色和蛋白质免疫印迹分析显示，DLE和MC下调了脊髓中GRPR、IL-31受体A和磷酸化STAT3的表达，表明其对中枢瘙痒信号的调节作用。此外，DLE和MC抑制了血清和皮肤组织中IL-31的水平。这些发现表明，DLE和MC可能通过多种机制缓解瘙痒，包括肥大细胞稳定、组胺减少和中枢瘙痒途径的调节。DLE和MC的广谱止痒活性突出了它们作为多种瘙痒性疾病天然治疗剂的潜力，为合成止痒药物提供了更安全的替代品。有必要进行进一步研究以在临床环境中验证这些发现，并阐明其疗效背后的分子机制。
