天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (增刊2): 107-113.

• 数据研究 • 上一篇    下一篇

基于网络药理学及分子对接探究山柰酚调控PI3K/AKT信号通路治疗骨质疏松的潜在机制

王慧玺1,罗峥伟1,赵灿斌2,孙宏章1,陈东峰3,李晓阳3,管东辉3*   

  • 出版日期:2024-12-09 发布日期:2024-12-09
  • 基金资助:
    山东省自然科学基金(ZR2022MH147);山东省中医药科技发展项目(2020Q016)

Potential mechanism of kaempferol on the regulation of PI3K/AKT signaling pathway for the treatment of osteoporosis based on network pharmacology and molecular docking

WANG Hui-xi1,LUO Zheng-wei1,ZHAO Can-bin2,SUN Hong-zhang1,CHEN Dong-feng3,LI Xiao-yang3,GUAN Dong-hui3*   

  1. 1The First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,China;2The First Clinical Medical College,Guangxi University of Traditional Chinese Medicine,Nanning 530200,China;3Department of Orthopedics,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China
  • Online:2024-12-09 Published:2024-12-09

摘要: 基于网络药理学及分子对接探讨山柰酚治疗骨质疏松症的治疗作用,并初步探究其潜在作用机制。通过数据挖掘形式寻找山柰酚的2D结构式并进行初步筛选,将符合条件的化合物进行预测靶点,同时挖掘对骨质疏松的靶点数据进行预测后取交集,制作蛋白质互作网络,进行GO、DO、KEGG网络分析,并筛选出核心蛋白,对所得靶点及药物中化合物进行分子对接验证。通过数据库挖掘并进行degree值排序后得到山柰酚靶点99个、骨质疏松靶点5 937个,得到PPI网络发现AKT1、GSK3B、PIK3CG、PIK3R1四个点位度值较大处于较核心位置。GO富集分析发现生物过程中涉及大量对刺激的反应及磷酸化过程,其中生物过程涉及磷酸盐代谢过程的调节、对磷代谢过程的调节作用,分子功能涉及磷酸转移酶活性、转移含磷基团核受体活性;DO显示骨与关节疾病的基因富集于第10位,较为靠前的位置;KEGG结果显示,较大数量靶点富集在于癌症、肿瘤相关通路,其中包括PI3K/AKT信号通路相关靶点。分子对接结果表明山柰酚与AKT1、GSK3B、PIK3R1、PIK3CG均能形成多条氢键并存在较强结合能。以上结果表明,山柰酚具有多靶点调控的优势,可能通过调控PI3K/AKT信号通路的相关基因及干预蛋白的表达,来发挥对骨质疏松症的治疗作用。

关键词: 山柰酚, 骨质疏松, 网络药理学, 分子对接, PI3K/AKT信号通路

Abstract:

In this study,the therapeutic efficacy of kaempferol in the management of osteoporosis was scrutinized through the integration of network pharmacology and molecular docking techniques,with an initial foray into elucidating its underlying mechanism.Within the context of this paper,an extensive search for the two-dimensional structural formula of kaempferol was conducted,followed by a preliminary screening of potential compounds via data mining,which were subsequentially predicted as putative targets.Concurrently,protein-protein interaction networks were meticulously constructed through the exploitation of osteoporosis-related target data for predictive analysis.An in-depth examination of GO,DO,and KEGG pathways was performed.The pivotal protein nodes were identified,and the veracity of the target compound within the pharmacological agent was substantiated through molecular docking.Through comprehensive database mining and degree-based ranking,a total of 99 kaempferol targets and 5 937 osteoporosis targets were ascertained.Within the PPI network,the central nodes AKT1,GSK3B,PIK3CG,and PIK3R1 were observed to occupy prominence with elevated degree values.GO enrichment analysis revealed a preponderance of biological processes responsive to stimuli and phosphorylation events,inclusive of the regulation of phosphate metabolism,phosphorus metabolism regulation,and the phosphotransferase activity and nuclear receptor activity associated with the conveyance of phosphorous groups under molecular function.The DO analysis indicated that genes pertained to bone and joint disorders were significantly enriched within the 10th percentile,signifying notable proximity to the forefront.KEGG pathway analysis disclosed a substantial enrichment of targets within pathways associated with cancer and tumorigenesis,encompassing those pertinent to the PI3K/AKT signaling pathway.Molecular docking results demonstrated that kaempferol could form multiple hydrogen bonds with AKT1, GSK3B, PIK3R1, and PIK3CG, and had strong binding energy. The above results indicated that kaempferol possessed the advantage of multi-target regulation, and might have exerted therapeutic effects on osteoporosis by regulating the expression of related genes and interventional proteins in the PI3K/AKT signaling pathway.

Key words: kaempferol, osteoporosis, network pharmacology, molecular docking, PI3K/AKT signaling pathway

中图分类号:  R274.9