文献类型：期刊文献

英文题名：Proteomic Profiling of Qi-blood Deficiency vs Damp-heat Syndrome in Colorectal Cancer : Therapeutic Targeting by Astragaloside IV-berberine

作者：Li, Zhao-Huan[1,2];Zhao, Jing-Wen[3];Zhang, Xin[1];Guo, Jian-Jin[4];Xu, Jie[5];Yang, Zeng-Qiang[2];Tu, Hao[6];Zou, Min[2];Gui, Ming-Bin[7,8];Gao, Feng[1,2]

第一作者：Li, Zhao-Huan

通信作者：Gao, F[1];Gao, F[2];Gui, MB[3];Gui, MB[4]

机构：[1]Gansu Univ Chinese Med, Sch Clin Chinese Med, Lanzhou 730101, Peoples R China;[2]Gansu Prov Cent Hosp, Dept Colorectal & Anal Surg, Lanzhou 730050, Peoples R China;[3]Xian Hosp Tradit Chinese Med, Dept Colorectal & Anal Surg, Xian 710021, Peoples R China;[4]Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Nat Prod Chem, Lanzhou 730000, Peoples R China;[5]Jilin Univ, Hosp 1, Dept Hepatobiliary & Pancreat Surg 1, Changchun 130021, Peoples R China;[6]Chongqing Qijiang Dist People s Hosp, Dept Colorectal Surg, Chongqing 401420, Peoples R China;[7]Chinese People s Liberat Army, Hosp Joint Logist Support Force 940, Dept Colorectal & Anal Surg, Lanzhou 730050, Peoples R China;[8]Chinese People s Liberat Army, th Hosp Joint Logist Support Force 940, Key Lab Stem Cells & Gene Drugs Gansu Prov, Lanzhou 730050, 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 730101, Peoples R China;[2]corresponding author), Gansu Prov Cent Hosp, Dept Colorectal & Anal Surg, Lanzhou 730050, Peoples R China;[3]corresponding author), Chinese People s Liberat Army, Hosp Joint Logist Support Force 940, Dept Colorectal & Anal Surg, Lanzhou 730050, Peoples R China;[4]corresponding author), Chinese People s Liberat Army, th Hosp Joint Logist Support Force 940, Key Lab Stem Cells & Gene Drugs Gansu Prov, Lanzhou 730050, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：53

期号：9

起止页码：2462

外文期刊名：PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001889858900006)】；

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

语种：英文

外文关键词：colorectal cancer; qi-blood deficiency syndrome; damp-heat syndrome; proteomics; astragaloside IV; berberine

摘要：Objective Colorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a "syndrome-differential protein-herbal component" network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. Methods Tumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the antiproliferative activities of these compounds in vitro. Results A total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF-kappa B signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than-5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC50 value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. Conclusion CRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.