Liu Jianzeng, Xu Xiaohao, Jian Mengqiong, Guo Yonggang, Zhai Lu, Sun Guang, Sun Liwei, Jiang Rui
Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, 130117, China.
Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin Province, 130021, China.
J Ethnopharmacol. 2025 Jun 12;349:119948. doi: 10.1016/j.jep.2025.119948. Epub 2025 May 9.
Glycyrrhiza glabra. L is a traditional herbal medicine widely recognized for its skin-whitening properties; however, the specific active compounds and underlying molecular mechanisms responsible for these effects remain largely uncharacterized.
To identify the bioactive constituents in G. glabra extract (GGE) responsible for its depigmenting effects and to elucidate the molecular mechanisms underlying their skin-whitening activity.
The depigmenting activity of GGE was assessed through NaOH lysis, DOPA oxidation assays, and high-performance liquid chromatography for component identification. Network pharmacology, western blotting, immunohistochemistry, and immunofluorescence were performed to investigate the effects of glabridin on pigmentation-related targets.
Among the tested extracts, the 80 % ethanol extract of G. glabra (GGE80) exhibited the most potent inhibition of mushroom tyrosinase (TYR) activity in vitro, along with significantly reduced melanin content and TYR activity in B16F10 melanoma cells. GGE80 also suppressed melanin accumulation and downregulated the key melanogenesis-associated proteins. Seven major compounds were identified in GGE80: liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, 18β-glycyrrhetinic acid, and glabridin. Among these, liquiritin, isoliquiritigenin and glabridin were identified as the primary melanin-inhibitory agents. Of these, glabridin demonstrated the most potent, activity in both in vivo and in vitro models. Network pharmacology analysis revealed that glabridin targeted MITF, a central transcription factor regulating melanogenic enzymes. Mechanistic studies further indicated that glabridin reduced CREB phosphorylation and SOX10 protein expression, both critical regulators of MITF transcription. Additionally, glabridin inhibited the nuclear translocation of CRTC1, a CREB-regulated transcription coactivator, leading to its cytoplasmic retention and phosphorylation.
The GGE80 demonstrated the most significant whitening effects. Among its constituents, glabridin was identified as the key active compound responsible for inhibiting melanogenesis. Mechanistically, glabridin exerts its effects by suppressing CREB/CRTC1-mediated transcriptional activation of MITF.
光果甘草是一种传统草药，其美白特性广为人知；然而，导致这些作用的具体活性成分和潜在分子机制在很大程度上仍未明确。
鉴定光果甘草提取物（GGE）中具有色素脱除作用的生物活性成分，并阐明其美白活性的分子机制。
通过氢氧化钠裂解、多巴氧化测定以及用于成分鉴定的高效液相色谱法评估GGE的色素脱除活性。进行网络药理学、蛋白质免疫印迹、免疫组织化学和免疫荧光实验以研究光甘草定对色素沉着相关靶点的影响。
在测试的提取物中，光果甘草80%乙醇提取物（GGE80）在体外对蘑菇酪氨酸酶（TYR）活性表现出最有效的抑制作用，同时显著降低了B16F10黑色素瘤细胞中的黑色素含量和TYR活性。GGE80还抑制了黑色素积累并下调了关键的黑色素生成相关蛋白。在GGE80中鉴定出七种主要化合物：甘草苷、异甘草苷、甘草素、异甘草素、甘草酸、18β-甘草次酸和光甘草定。其中，甘草苷、异甘草素和光甘草定被确定为主要的黑色素抑制剂。其中，光甘草定在体内和体外模型中均表现出最有效的活性。网络药理学分析表明，光甘草定靶向MITF，这是一种调节黑色素生成酶的核心转录因子。机制研究进一步表明，光甘草定降低了CREB磷酸化和SOX10蛋白表达，二者均为MITF转录的关键调节因子。此外，光甘草定抑制了CRTC1（一种CREB调节的转录共激活因子）的核转位，导致其在细胞质中滞留并磷酸化。
GGE80表现出最显著的美白效果。在其成分中，光甘草定被确定为抑制黑色素生成的关键活性化合物。从机制上讲，光甘草定通过抑制CREB/CRTC1介导的MITF转录激活发挥作用。
