Division of Life Science, Centre for Chinese Medicine, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
J Ethnopharmacol. 2024 Nov 15;334:118585. doi: 10.1016/j.jep.2024.118585. Epub 2024 Jul 15.
Alopecia, or hair loss, refers to ongoing decline of mature hair on the scalp or any other region of the body. Fructus Sophorae, a fruit from Sophora japonica L., contains various phytochemicals, e.g., sophoricoside, that exhibit a broad range of pharmacological effects. The potential functions of herbal extracts deriving from Fructus Sophorae and/or its major phytochemical, sophoricoside, in treating alopecia are probed here.
The objective was to determine the ability of Fructus Sophorae extract and sophoricoside in promoting hair growth and it signalling mechanism.
Molecular docking studies were conducted to measure the binding affinities between sophoricoside and M4 mAChR in the allosteric binding site. The mechanism of Fructus Sophorae and sophoricoside in activating the signalling involving Wnt/β-catenin and muscarinic AChR was evaluated by using immortalized human dermal papilla cell line (DPC), as well as their roles in promoting hair growth. The activity of pTOPflash-luciferase in transfected DPCs was used to examine the transcriptional regulation of Wnt/β-catenin-mediated genes. RT-PCR was applied to quantify mRNA expressions of the biomarkers in DPCs responsible for hair growth. The phosphorylated protein levels of Wnt/β-catenin and PI3K/AKT in DPC were revealed by using Western blot analysis. The culture of ex vivo mouse vibrissae hair follicle was used to evaluate the hair growth after the treatments.
The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/β-catenin signalling. The result of molecular docking showed a high binding affinity between sophoricoside and M4 mAChR. The effect of sophoricoside was blocked by specific inhibitor of M4 mAChR, but not by other inhibitors of mAChRs. Sophoricoside promoted hair growth in cultured ex vivo mouse vibrissae hair follicle by acting through M4 mAChR.
The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/β-catenin signalling via activation of M4 mAChR. The results suggested beneficial functions of Fructus Sophorae and sophoricoside as a potential candidate in treating alopecia.
脱发是指头皮或身体其他部位的成熟毛发持续减少。槐果，是槐属植物槐的果实，含有多种植物化学物质，如槐定碱，具有广泛的药理作用。本文探讨了槐果及其主要植物化学物质槐定碱提取物在治疗脱发方面的潜在功能。
本研究旨在确定槐果提取物和槐定碱促进毛发生长的能力及其信号机制。
采用分子对接研究槐定碱与 M4 mAChR 变构结合位点的结合亲和力。通过永生化人真皮乳头细胞系（DPC）评估槐果和槐定碱激活涉及 Wnt/β-catenin 和毒蕈碱型乙酰胆碱受体（mAChR）信号通路的机制，以及它们在促进毛发生长中的作用。转染 DPC 的 pTOPflash-荧光素酶活性用于检测 Wnt/β-catenin 介导基因的转录调控。应用 RT-PCR 定量分析负责毛发生长的 DPC 中生物标志物的 mRNA 表达。用 Western blot 分析揭示 DPC 中 Wnt/β-catenin 和 PI3K/AKT 的磷酸化蛋白水平。采用体外培养小鼠触须毛囊评估治疗后的毛发生长情况。
槐果乙醇提取物和槐定碱激活了 Wnt/β-catenin 信号通路。分子对接结果显示槐定碱与 M4 mAChR 具有高结合亲和力。M4 mAChR 的特异性抑制剂可阻断槐定碱的作用，但其他 mAChR 抑制剂则不能。槐定碱通过作用于 M4 mAChR 促进体外培养的小鼠触须毛囊的毛发生长。
槐果乙醇提取物和槐定碱通过激活 M4 mAChR 激活 Wnt/β-catenin 信号通路。结果表明槐果和槐定碱作为治疗脱发的潜在候选药物具有有益作用。
