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Astragali radix Against Colorectal Cancer: Network Pharmacology, Molecular Docking, and In Vitro/In Vivo Validation of PI3K-Akt Pathway Modulation  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:Astragali radix Against Colorectal Cancer: Network Pharmacology, Molecular Docking, and In Vitro/In Vivo Validation of PI3K-Akt Pathway Modulation

作者:Li, Zhaohuan[1,2];Guo, Jianjin[3];Gui, Mingbin[4];Xu, Jie[5];Zhao, Jingwen[6];Zhang, Xin[1];Zhang, Yansheng[7];Yang, Zijie[2];Yang, Zengqiang[2];Gao, Feng[1,2]

第一作者:Li, Zhaohuan

通信作者:Gao, F[1];Yang, ZQ[2];Gao, F[2]

机构:[1]Gansu Univ Chinese Med, Sch Clin Chinese Med, Lanzhou, Peoples R China;[2]Gansu Prov Cent Hosp, Dept Colorectal & Anal Surg, Lanzhou, Peoples R China;[3]Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Nat Prod Chem, Lanzhou, Peoples R China;[4]Chinese Peoples Liberat Army, Hosp Joint Logist Support Force 940, Dept Colorectal & Anal Surg, Lanzhou, Peoples R China;[5]First Hosp Jilin Univ, Dept Hepatobiliary & Pancreat Surg 1, Changchun, Peoples R China;[6]Xian Hosp Tradit Chinese Med, Dept Colorectal & Anal Surg, Xian, Peoples R China;[7]Gansu Prov Matern & Child Care Hosp, Dept Breast Surg 1, Lanzhou, Peoples R China

第一机构:甘肃中医药大学

通信机构:[1]corresponding author), Gansu Univ Chinese Med, Sch Clin Chinese Med, Lanzhou, Peoples R China;[2]corresponding author), Gansu Prov Cent Hosp, Dept Colorectal & Anal Surg, Lanzhou, Peoples R China.|[10735]甘肃中医药大学;

年份:2026

外文期刊名:PHYTOTHERAPY RESEARCH

收录:;Scopus(收录号:2-s2.0-105034142818);WOS:【SCI-EXPANDED(收录号:WOS:001724985300001)】;

基金:This work was supported by the Gansu Provincial Natural Science Foundation (Key Research and Development Program Project, Grant 20YF8FA098; Basic Research Program Project, Grant 23JRRA539), the Gansu Provincial Youth Science and Technology Fund (Grant 25JRRA429), and the Lanzhou Municipal Science and Technology Bureau Project (Grant 2024-9-163).

语种:英文

外文关键词:Astragali radix; colorectal cancer; in vitro and in vivo mechanisms; molecular docking; network pharmacology; PI3K-Akt signaling pathway

摘要:Colorectal cancer (CRC) exhibits high incidence and mortality rates, and current therapeutic approaches remain limited, underscoring the urgent need for novel treatment strategies. Astragali Radix, a traditional Chinese medicine with diverse pharmacological properties, has shown potential in cancer therapy; however, its anti-CRC mechanisms remain poorly understood. This study investigated the active components of A. Radix and their anti-CRC mechanisms using an integrated approach combining network pharmacology, molecular docking, and in vitro and in vivo experiments. Twenty active components of A. Radix with high oral bioavailability and drug-likeness were screened from databases, and relevant networks were constructed to identify core targets, including SRC, PIK3CA, and AKT1. Enrichment analysis revealed that these targets are primarily involved in the regulation of the PI3K-Akt signaling pathway. Molecular docking confirmed strong binding affinity between the active components of A. Radix and the core targets. In vitro experiments on HCT 116 and HT 29 cells demonstrated that A. Radix and quercetin inhibited cell proliferation in a concentration- and time-dependent manner, downregulating the mRNA expression of key genes (PIK3CA, PIK3R1, AKT1) in the PI3K-Akt pathway, and A. Radix showed superior efficacy compared with quercetin. Western blot analysis confirmed that the protein levels of PI3K, p-PI3K, AKT, p-AKT, PIK3CA, PIK3R1, and AKT1 were reduced in A. Radix-treated cells, as were the ratios of p-PI3K/PI3K and p-AKT/AKT. In vivo experiments on MC38 tumor-bearing mice further revealed that A. Radix significantly suppressed tumor growth and reduced pathway-related protein levels, outperforming quercetin. Additionally, acute toxicity experiments confirmed the favorable safety profile of A. Radix. This study demonstrates that A. Radix inhibits tumor cell proliferation through multi-component targeting of the PI3K-Akt signaling pathway, providing new therapeutic targets and theoretical evidence for CRC treatment. Furthermore, it establishes a methodological framework for the modern investigation of traditional Chinese medicine formulations.

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