通过网络药理学方法筛选催乳丸调治缺乳的主要活性成分和潜在靶点蛋白,构建有效成分-蛋白相互作用网络,采用计算机模拟方法开展分子对接验证,探讨催乳丸调治缺乳的潜在分子机制。经筛选,催乳丸中主要包括槲皮素、木犀草素、山奈酚、香叶木素、叶酸、β-谷甾醇等12个活性成分;药物与疾病靶点的交集包括STAT3、MAPK1、JAK2、EGFR、ESR1、STAT5A等16个关键蛋白靶点;经过富集分析和筛选,发现与催乳丸活性成分作用的靶点蛋白富集在催乳素信号通路、雌激素信号通路、AMPK信号通路、cAMP信号通路等多种生物学过程。分子对接结果显示,槲皮素、β-谷甾醇、木犀草素与关键靶点STAT3、MAPK1、ESR1、EGFR的结合能力较强,其通过调控转录因子、激酶、雌激素受体蛋白和表皮生长因子受体蛋白,影响乳腺上皮细胞生长,发挥调治缺乳作用。研究结果初步揭示了催乳丸治疗缺乳的多组分、多靶点、多途径机制,为缺乳症状的治疗研究提供了参考。
LI Mengting1
,
SHI Lin1
,
HOU Chen1
,
YU Meng2
,
LI Jianke1*
. 基于网络药理学和分子对接的催乳丸调治缺乳作用机制[J]. 陕西师范大学学报(自然科学版), 2023
, 51(3)
: 75
-85
.
DOI: 10.15983/j.cnki.jsnu.2023206
To investigate the potential molecular mechanism of galactopoietic pill in the treatment of hypogalactia, the main active components and their potential target proteins in hypogalactia treatment were profiled in this study with the aid of the network pharmacology.The active component-protein interaction network was constructed, and the molecular docking verification was carried out by computer simulation. Results showed that galactopoietic pill mainly includes twelve bioactive components (quercetin, luteolin, geranitin, kaempferol, folic acid, β-sitosterol, etc.) and sixteen key target proteins (STAT3, MAPK1, JAK2, EGFR, ESR1, STAT5A, etc.). The enrichment analysis and screening illustrated that the target proteins of the active components in galactopoietic pill are enriched in multiple biological pathways, such as prolactin signaling pathway, estrogen signaling pathway, AMPK signaling pathway and cAMP signaling pathway. The molecular docking verification showed that quercetin, β-sitosterol and luteolin have strong binding ability with STAT3, MAPK1, ESR1 and EGFR, which affect the growth of mammary epithelial cells and play a key role in hypogalactia treatment by regulating transcription factors, kinases, estrogen receptor proteins and epidermal growth factor receptor proteins. The results preliminarily reveal the multi-components, multi-targets and multi-pathways mechanism of galactopoietic pill in hypogalactia treatment and provide a reference for hypogalactia treatment.