NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2024, Vol. 36 ›› Issue (增刊2): 107-113.

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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

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

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