{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:35Z","timestamp":1785434855656,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Natural Science Foundation of China","doi-asserted-by":"publisher","award":["QC2025C025"],"award-info":[{"award-number":["QC2025C025"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heilongjiang Provincial Department of Education Basic Scientific Research Operating Fund","award":["2023-KYYWF-0576"],"award-info":[{"award-number":["2023-KYYWF-0576"]}]},{"name":"Jiamusi University Doctoral Special Scientific Research Fund Startup Project","award":["JMSUBZ22-05"],"award-info":[{"award-number":["JMSUBZ22-05"]}]},{"award":["JMSUBZ22-05"],"award-info":[{"award-number":["JMSUBZ22-05"]}],"id":[{"id":"https:\/\/ror.org\/01vasff55","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Wild soybean (Glycine soja), as the wild ancestor of cultivated soybean, serves as a rich reservoir of phytochemicals with significant potential in functional food applications and chemoprevention. However, its metabolic characteristics and health benefits remain to be systematically elucidated. In this study, non-targeted metabolomics technology was employed, in conjunction with network pharmacology and molecular docking analysis, to systematically investigate the metabolic differences between wild soybean seeds from three distinct ecological regions and cultivated soybean seeds. Metabolomic profiling revealed the unique metabolic characteristics of wild soybean, identifying 124 significantly upregulated metabolites and 7 unique compounds, with the most notable enrichment in flavonoids and prunolides. Network pharmacology analysis indicated that 22 key metabolites in wild soybeans were associated with 503 pan-cancer targets (covering breast, lung, and colorectal cancers), primarily regulating pathways related to \u201ccancer\u201d and \u201clipids and atherosclerosis.\u201d Molecular docking experiments further confirmed the stable binding affinity of key bioactive components, including quercetin and L-arginine, with core targets such as TP53, TNF, EGFR, IL1B, and JUN. These findings elucidate the unique phytochemical profile of wild soybean and its potential multi-target chemopreventive mechanisms, providing theoretical support for developing it as a natural chemopreventive agent.<\/jats:p>","DOI":"10.3390\/foods15071209","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:51:03Z","timestamp":1775130663000},"page":"1209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Metabolomics and Network Pharmacology Study Reveals Chemopreventive Potential of Wild Soybean (Glycine soja)"],"prefix":"10.3390","volume":"15","author":[{"given":"Meinan","family":"Sui","sequence":"first","affiliation":[{"name":"College of Biology and Agriculture, Jiamusi University, Jiamusi 154007, China"},{"name":"Heilongjiang Institute of Pharmacy, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Biology and Agriculture, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Biology and Agriculture, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejiang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Biology and Agriculture, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi 154000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Heilongjiang Institute of Pharmacy, Jiamusi 154007, China"},{"name":"College of Pharmacy, Jiamusi University, Jiamusi 154007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115207","DOI":"10.1016\/j.lwt.2023.115207","article-title":"Changes in isoflavone profile, antioxidant activity, and phenolic contents in taiwanese and canadian soybeans during tempeh processing","volume":"186","author":"Liu","year":"2023","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/pbi.14541","article-title":"An r2r3-type myb transcription factor, gmmyb77, negatively regulates isoflavone accumulation in soybean [Glycine max (L.) Merr.]","volume":"23","author":"Liu","year":"2024","journal-title":"Plant Biotechnol. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118850","DOI":"10.1016\/j.jep.2024.118850","article-title":"Hepatoprotective action mechanism and quantification of soyasaponin bb in abri herba by hplc and network pharmacology","volume":"337","author":"Lin","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9250620","DOI":"10.26599\/FSHW.2025.9250620","article-title":"A rapid analysis method to discover antioxidant active components and mechanisms in soybean: Untargeted metabolomics combined with network pharmacology and spectrum-effect relationship-component knockout-identification techniques","volume":"14","author":"Liu","year":"2025","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Park, S.H., Seo, J.H., Kim, M.Y., Yun, H.J., Kang, B.K., Kim, J.H., Heo, S.V., Lee, Y.H., Park, H.R., and Choi, M.S. (2025). Enhanced antitumor activity of korean black soybean cultivar \u2018soman\u2019 by targeting stat-mediated aerobic glycolysis. Antioxidants, 14.","DOI":"10.3390\/antiox14020228"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9662","DOI":"10.1021\/acs.jafc.5c00695","article-title":"Soybean sprout peptides alleviate obesity via pi3k-akt and jak-stat pathway modulation, gut microbiota regulation, and metabolic reprogramming","volume":"73","author":"Wu","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1021\/acs.jafc.3c08202","article-title":"Multiomics analyses reveal the dual role of flavonoids in pigmentation and abiotic stress tolerance of soybean seeds","volume":"72","author":"Jiang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109290","DOI":"10.1016\/j.foodres.2020.109290","article-title":"Comparative metabolic profiling of cultivated and wild black soybeans reveals distinct metabolic alterations associated with their domestication","volume":"134","author":"Hyeon","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139883","DOI":"10.1016\/j.foodchem.2024.139883","article-title":"Flavonoid localization in soybean seeds: Comparative analysis of wild (Glycine soja) and cultivated (Glycine max) varieties","volume":"456","author":"Ren","year":"2024","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chen, Q., Wang, X., Yuan, X., Shi, J., Zhang, C., Yan, N., and Jing, C. (2021). Comparison of phenolic and flavonoid compound profiles and antioxidant and \u03b1-glucosidase inhibition properties of cultivated soybean (Glycine max) and wild soybean (Glycine soja). Plants, 10.","DOI":"10.3390\/plants10040813"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1111\/ppl.12870","article-title":"Differential responses of molecular mechanisms and physiochemical characters in wild and cultivated soybeans against invasion by the pathogenic Fusarium oxysporum Schltdl","volume":"166","author":"Chang","year":"2018","journal-title":"Physiol. Plant."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, X., Li, S., Wang, J., Chen, G., Tao, X., and Xu, S. (2023). Metabolomic analysis reveals domestication-driven reshaping of polyphenolic antioxidants in soybean seeds. Antioxidants, 12.","DOI":"10.3390\/antiox12040912"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tareq, F.S., Kotha, R.R., Natarajan, S., Sun, J., and Luthria, D.L. (2023). An untargeted metabolomics approach to study the variation between wild and cultivated soybeans. Molecules, 28.","DOI":"10.3390\/molecules28145507"},{"key":"ref_14","first-page":"209","article-title":"Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/S0140-6736(19)30041-8","article-title":"Health effects of dietary risks in 195 countries, 1990\u20132017: A systematic analysis for the global burden of disease study 2017","volume":"393","author":"Afshin","year":"2019","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41592-021-01197-1","article-title":"Mass spectrometry-based metabolomics: A guide for annotation, quantification and best reporting practices","volume":"18","author":"Alseekh","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nprot.2012.135","article-title":"Global metabolic profiling of animal and human tissues via uplc-ms","volume":"8","author":"Want","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"Ms-dial: Data-independent ms\/ms deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tang, C., Li, X., Wang, T., Wang, J., Xiao, M., He, M., Chang, X., Fan, Y., and Li, Y. (2023). Characterization of metabolite landscape distinguishes medicinal fungus cordyceps sinensis and other cordyceps by uhplc-q exactive hf-x untargeted metabolomics. Molecules, 28.","DOI":"10.3390\/molecules28237745"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"An, J., Sun, L., Liu, M., Dai, R., Si, Q., Ge, G., Wang, Z., and Jia, Y. (2024). Mechanistic insights into nitrite degradation by metabolites of L. plantarum a50: An LC-MS-based untargeted metabolomics analysis. Fermentation, 10.","DOI":"10.3390\/fermentation10020092"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105934","DOI":"10.1016\/j.fbio.2025.105934","article-title":"Integrative analysis of metabolite changes and potential health effects in pomegranate juice fermentation","volume":"64","author":"He","year":"2025","journal-title":"Food Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116443","DOI":"10.1016\/j.foodres.2025.116443","article-title":"Metabolomics combined with network pharmacology reveals the regional and variety heterogeneity of grape metabolites and their potential antioxidant mechanisms","volume":"211","author":"Fei","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nbt.3096","article-title":"Resequencing 302 wild and cultivated accessions identifies genes related to domestication and improvement in soybean","volume":"33","author":"Zhou","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107457","DOI":"10.1016\/j.phrs.2024.107457","article-title":"Flavonoids and their derivatives as DNA topoisomerase inhibitors with anti-cancer activity in various cell models: Exploring a novel mode of action","volume":"209","author":"Sitarek","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1111\/pbi.14349","article-title":"Soybean steroids improve crop abiotic stress tolerance and increase yield","volume":"22","author":"Yu","year":"2024","journal-title":"Plant Biotechnol. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hong, R., Lim, S.-C., Lee, T.-B., and Han, S.-I. (2023). Anticancer effect of gallic acid on acidity-induced invasion of mcf7 breast cancer cells. Nutrients, 15.","DOI":"10.3390\/nu15163596"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155615","DOI":"10.1016\/j.phymed.2024.155615","article-title":"Gentisic acid prevents colorectal cancer metastasis via blocking gpr81-mediated depdc5 degradation","volume":"129","author":"Feng","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-023-01347-1","article-title":"Targeting p53 pathways: Mechanisms, structures and advances in therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70220","DOI":"10.1002\/ddr.70220","article-title":"Overcoming resistance in egfr-mutant cancers: A comprehensive review of inhibitor evolution and sar-based design","volume":"87","author":"Naykwadi","year":"2026","journal-title":"Drug Dev. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling pathways of the tnf superfamily: A double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.36922\/CP025310046","article-title":"Interleukin-1 beta signaling in cancer: A double-edged sword in inflammation and tumorigenesis","volume":"7","author":"Yilmaz","year":"2025","journal-title":"Cancer Plus"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jafri, Z., Li, Y., Zhang, J., O\u2019Meara, C.H., and Khachigian, L.M. (2025). Jun, an oncological foe or friend?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020555"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1155\/jcpt\/2635281","article-title":"Quercetin modulates the p53 signaling pathway to induce apoptosis: Combating vemurafenib resistance in melanoma","volume":"2025","author":"Huang","year":"2025","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1136\/gutjnl-2024-333020","article-title":"Fasting-mimicking diet-enriched bifidobacterium pseudolongum suppresses colorectal cancer by inducing memory cd8+ t cells","volume":"74","author":"Nan","year":"2025","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hannemann, J., Oliveira-Ferrer, L., Goele, A.K., Mileva, Y., Kleinsang, F., R\u00f6glin, A., Witzel, I., M\u00fcller, V., and B\u00f6ger, R. (2025). L-arginine dependence of breast cancer\u2013molecular subtypes matter. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13908-4"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103940","DOI":"10.1016\/j.drudis.2024.103940","article-title":"Treating liver cancer through arginine depletion","volume":"29","author":"Prasad","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mustafa, M., Ahmad, R., Tantry, I.Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Hassan, M.I., and Habib, S. (2024). Apoptosis: A comprehensive overview of signaling pathways, morphological changes, and physiological significance and therapeutic implications. Cells, 13.","DOI":"10.3390\/cells13221838"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Racacho, K.J., Shiau, Y.-P., Villa, R., Mahri, S., Tang, M., Lin, T.-Y., and Li, Y. (2025). The tumor immune microenvironment: Implications for cancer immunotherapy, treatment strategies, and monitoring approaches. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1621812"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s42003-025-07547-5","article-title":"Quercetin alleviates endothelial dysfunction in preeclampsia by inhibiting ferroptosis and inflammation through egfr binding","volume":"8","author":"Shi","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Boreak, N., Almasoudi, S.A., Alharbi, A., Judayba, M., Tahrei, S., Eishah, A.A., Madkhali, T.A., Hattan, M.A., Majrashi, M.H., and Daak, H.A. (2025). Molecular docking and md simulations predicted quercetin as a potent human interleukin-1 beta (hil1\u03b2) inhibitor for improved endodontic disease management. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0336841"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1007\/s00210-023-02870-2","article-title":"Quercetin, a key active ingredient of Jianpi Zishen Xiehuo Formula, suppresses M1 macrophage polarization and platelet phagocytosis by inhibiting STAT3 activation based on network pharmacology","volume":"397","author":"Wang","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Guan, H., Zhang, W., Liu, H., Jiang, Y., Li, F., Wu, M., Waterhouse, G.I.N., Sun-Waterhouse, D., and Li, D. (2023). Quercetin induces apoptosis in hepg2 cells via directly interacting with yy1 to disrupt yy1-p53 interaction. Metabolites, 13.","DOI":"10.3390\/metabo13020229"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1128\/CVI.13.3.319-328.2006","article-title":"The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the nf-\u03ba\u03b2 system","volume":"13","author":"Nair","year":"2006","journal-title":"Clin. Vaccine Immunol."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/7\/1209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T12:18:27Z","timestamp":1775132307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/7\/1209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["foods15071209"],"URL":"https:\/\/doi.org\/10.3390\/foods15071209","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}