School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.
School of Food and Bioengineering, Xihua University, Chengdu, Sichuan 610039, China.
Biomed Res Int. 2022 Nov 18;2022:3139123. doi: 10.1155/2022/3139123. eCollection 2022.
The aim of the present study was to explore the potential pharmacological mechanism of baicalin by combining network pharmacology prediction and the experimental verification of alopecia. Networks of baicalin-associated targets and alopecia-related genes were constructed using the STRING database. Potential targets and pathways associated with the therapeutic efficacy of baicalin were identified via enrichment analysis using Cytoscape and the database for annotation, visualization and integrated discovery (Metascape). The back hair of C57BL/6J mice was removed with depilatory cream to verify the therapeutic effect of baicalin. Human hair dermal papilla cells (HHDPCs) were used to explore the mechanism of action of baicalin. Network pharmacology analysis revealed that the potential targets of baicalin mainly include protein serine/threonine kinase, Src protein, epidermal growth factor receptor, and insulin-like growth factor 1 (IGF1), which were indicated to mediate neutrophil degranulation and regulation of cell-cell adhesion, vesicle lumen, cytoplasmic vesicle, membrane raft, and endopeptidase activity. Multiple pathways were identified, such as proteoglycans in cancer, PI3K/AKT, and forkhead box O signaling pathways. Following baicalin treatment for the experimental mice, the coverage, length, and weight of the hair increased in a baicalin dose-dependent manner. Moreover, the histological evaluation showed that the number of hair follicles increased after baicalin treatment and melanin formation were pronounced. In addition, baicalin induced an increase in the phosphorylated p-AKT, p-glycogen synthase kinase-3, p-PI3K, TGF-1, and vascular endothelial growth factor levels. Furthermore, the activation levels of key protein p-AKT were increased. Baicalin induced the proliferation of HHDPCs and significantly upregulated p-AKT, IGF1, and alkaline phosphatase. In conclusion, the present study revealed that the pharmacological mechanisms of baicalin in alopecia therapy were associated with the proliferation of DPCs, the activation of the AKT pathway, and the transmission of downstream signals, indicating that baicalin is a potential drug candidate for the clinical treatment of hair loss.
本研究旨在通过网络药理学预测和脱发的实验验证，探索黄芩苷的潜在药理机制。使用 STRING 数据库构建黄芩苷相关靶点和脱发相关基因网络。使用 Cytoscape 和数据库注释、可视化和综合发现（Metascape）进行富集分析，确定与黄芩苷治疗效果相关的潜在靶点和途径。使用脱毛膏去除 C57BL/6J 小鼠的背毛，验证黄芩苷的治疗效果。用人头皮毛囊细胞（HHDPC）探索黄芩苷的作用机制。网络药理学分析表明，黄芩苷的潜在靶点主要包括蛋白丝氨酸/苏氨酸激酶、Src 蛋白、表皮生长因子受体和胰岛素样生长因子 1（IGF1），这些靶点介导中性粒细胞脱颗粒和细胞-细胞黏附、小泡腔、细胞质小泡、膜筏和内肽酶活性的调节。鉴定出多个途径，如癌症中的蛋白聚糖、PI3K/AKT 和叉头框 O 信号通路。经黄芩苷处理实验小鼠后，毛发的覆盖率、长度和重量均呈黄芩苷剂量依赖性增加。此外，组织学评价表明，黄芩苷处理后毛囊数量增加，黑色素形成明显。此外，黄芩苷诱导磷酸化 p-AKT、p-糖原合酶激酶-3、p-PI3K、TGF-1 和血管内皮生长因子水平升高。此外，关键蛋白 p-AKT 的激活水平增加。黄芩苷诱导 HHDPC 增殖，并显著上调 p-AKT、IGF1 和碱性磷酸酶。综上所述，本研究表明，黄芩苷治疗脱发的药理机制与 DPC 的增殖、AKT 途径的激活和下游信号的转导有关，表明黄芩苷是治疗脱发的潜在候选药物。
