Ding Jian, Xue Qian, Guo Weizhen, Cheng Gang, Zhang Lu, Huang Tantan, Wu Di, Tong Jiabing, Yang Cheng, Gao Yating, Li Zegeng
Department of First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China.
Anhui University of Chinese Medicine, Hefei, 230038, China.
Sci Rep. 2025 Apr 8;15(1):12033. doi: 10.1038/s41598-025-94793-6.
This study explores the mechanisms of Astragaloside A (AS-A), a significant active ingredient in Astragalus, This traditional Chinese medicine is both a medication and a food, combating lung adenocarcinoma using network pharmacology, molecular docking, molecular dynamics, and experimental validation. A protein-protein interaction (PPI) network was developed, identifying 10 key targets, including STAT3 and AKT1. GO and KEGG enrichment analyses indicated that these targets primarily participated in biological processes and pathways, including oxidative stress and the PI3K-Akt signalling pathway. Molecular docking and dynamic simulation evaluated AS-A's binding mode and stability with key targets. In molecular docking, 14 key targets of the HIF-1 signalling pathway had different binding energies with AS-A, such as the binding energy of PIK3R1 being -9.3. Kinetic simulations indicated the stability of the protein-ligand complex, as evidenced by RMSD values ranging from 0.2 to 0.4 nm. RMSF analysis showed that the protein residue flexibility characteristics were stable, the Rg values were stable, the number of hydrogen bonds was 10-20, and the solvent-accessible surface area was stable. Cell experiments showed that AS-A could regulate the expression of key signalling molecules such as STAT3 and AKT in lung adenocarcinoma models. This study provides insights into the mechanism of AS-A in treating lung adenocarcinoma. It proposes a new direction for anticancer research in traditional Chinese medicines, especially medications and foods.
本研究利用网络药理学、分子对接、分子动力学和实验验证等方法,探索黄芪中重要活性成分黄芪甲苷(AS-A)对抗肺腺癌的机制。黄芪这种中药既是药物又是食物。构建了蛋白质-蛋白质相互作用(PPI)网络,确定了10个关键靶点,包括STAT3和AKT1。基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析表明,这些靶点主要参与包括氧化应激和PI3K-Akt信号通路在内的生物学过程和途径。分子对接和动态模拟评估了AS-A与关键靶点的结合模式和稳定性。在分子对接中,HIF-1信号通路的14个关键靶点与AS-A具有不同的结合能,如PIK3R1的结合能为-9.3。动力学模拟表明蛋白质-配体复合物的稳定性,均方根偏差(RMSD)值在0.2至0.4nm范围内证明了这一点。均方根波动(RMSF)分析表明蛋白质残基的柔韧性特征稳定,回旋半径(Rg)值稳定,氢键数量为10至20,溶剂可及表面积稳定。细胞实验表明,AS-A可以调节肺腺癌模型中关键信号分子如STAT3和AKT的表达。本研究为AS-A治疗肺腺癌的机制提供了见解。它为中药尤其是药食两用中药的抗癌研究提出了新的方向。