The mechanisms of melanogenesis inhibition by glabridin:molecular docking,PKA/MITF and MAPK/MITF pathways

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.

基于综合因素刺激的肠易激综合征模型构建方法学研究

为了建立一个建模周期短且符合IBS发病机制的模型,我们将慢性不可预知刺激与化学刺激相结合,建立一种新的肠易激综合征模型,并探讨其可行性。以慢性不可预测刺激为单因素模型,慢性不可预测刺激加冰醋酸刺激为综合因素模型。从体重增长率、基本食物消耗量、蔗糖消耗量、粪便颗粒数、Bristol分值、腹部回撤反射、旷场实验、高架十字迷宫试验、肠道运输时间、HE染色等一系列试验中分析了肠易激综合征模型的症状。结果显示,与单因素模型和对照组相比,综合因素组模型中的大鼠体重增加较少、食物消耗、蔗糖消耗减少、粪便颗粒数增加、Bristol评分和疼痛阈值下降、运动量大大减少。由于综合刺激对大鼠模型有明显的作用,综合因素组模型更加符合IBS复杂的发病机制,可用于建立有效的IBS模型。与雌性大鼠相比,雄性大鼠的造模效果明显。