Zhang Jian, Shen Wanyan, Liu Fanzhi, He Hehe, Han Shuquan, Luo Lina
GuiZhou Institute of Subtropical Crops, Guizhou Academy of Agricultural Sciences, Guiyang, China.
Research and Development Department, Guizhou Weikang Zifan Pharmaceutical Co., Ltd., Guiyang, China.
PLoS One. 2025 Jan 14;20(1):e0313743. doi: 10.1371/journal.pone.0313743. eCollection 2025.
Fracture disrupts the integrity and continuity of the bone, leading to symptoms such as pain, tenderness, swelling, and bruising. Rhizoma Musae is a medicinal material frequently utilized in the Miao ethnic region of Guizhou Province, China. However, its specific mechanism of action in treating fractures remains unknown. This study aimed to elucidate the chemical constituents of the ethanol extract of Rhizoma Musae (EERM) and investigate its fracture-healing mechanism using network pharmacology.
The chemical profile of EERM was characterized via UHPLC-Q-Exactive-MS/MS. Subsequently, a comprehensive network of compounds, targets, and pathways was constructed using network pharmacology approaches. The interactions between the active compounds of EERM and their targets were validated through molecular docking, molecular dynamics simulation and in vitro cell experiments.
EERM contained 522 identified compounds. Topological analysis of the protein-protein interaction (PPI) network identified 59 core targets, including key proteins like AKT1, IL-6, and EGFR, known for their anti-inflammatory properties and ability to enhance bone cell proliferation and differentiation. Gene Ontology analysis indicated the involvement of EERM in biological processes such as peptidyl-serine phosphorylation, response to xenobiotic stimulus, and nutrient level regulation. KEGG analysis suggested that EERM's mechanism may involve signaling pathways such as PI3K-Akt, lipid and atherosclerosis, EGFR tyrosine kinase inhibitor resistance, and MAPK pathways. Molecular docking and molecular dynamics simulations results demonstrated a strong binding affinity between the main compounds of EERM and key targets. In vitro cell experiments demonstrate that EERM enhances cell proliferation by upregulating the expression levels of EGFR and STAT3, while simultaneously downregulating AKT1 and CASP3.
This study investigates the potential active compounds of EERM and its key targets in regulating multiple pathways of fracture, leading to promoting bone cell proliferation. These results offer valuable insights for the future development and clinical application of Rhizoma Musae.
骨折会破坏骨骼的完整性和连续性，导致疼痛、压痛、肿胀和瘀伤等症状。芭蕉根是中国贵州省苗族地区常用的一种药材。然而，其治疗骨折的具体作用机制尚不清楚。本研究旨在阐明芭蕉根乙醇提取物（EERM）的化学成分，并利用网络药理学研究其促进骨折愈合的机制。
通过超高效液相色谱-四极杆-静电场轨道阱串联质谱（UHPLC-Q-Exactive-MS/MS）对EERM的化学特征进行表征。随后，利用网络药理学方法构建了化合物、靶点和通路的综合网络。通过分子对接、分子动力学模拟和体外细胞实验验证了EERM活性化合物与其靶点之间的相互作用。
EERM含有522种已鉴定的化合物。蛋白质-蛋白质相互作用（PPI）网络的拓扑分析确定了59个核心靶点，包括AKT1、IL-6和EGFR等关键蛋白，这些蛋白以其抗炎特性以及增强骨细胞增殖和分化的能力而闻名。基因本体分析表明EERM参与了肽基丝氨酸磷酸化、对外源生物刺激的反应和营养水平调节等生物过程。京都基因与基因组百科全书（KEGG）分析表明，EERM的作用机制可能涉及PI3K-Akt、脂质与动脉粥样硬化、EGFR酪氨酸激酶抑制剂抗性和丝裂原活化蛋白激酶（MAPK）等信号通路。分子对接和分子动力学模拟结果表明，EERM主要化合物与关键靶点之间具有很强的结合亲和力。体外细胞实验表明，EERM通过上调EGFR和信号转导与转录激活因子3（STAT3）的表达水平来增强细胞增殖，同时下调AKT1和半胱天冬酶3（CASP3）。
本研究探究了EERM的潜在活性化合物及其在调节骨折多种通路中的关键靶点，从而促进骨细胞增殖。这些结果为芭蕉根的未来开发和临床应用提供了有价值的见解。
