{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:31Z","timestamp":1788153511133,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Colorectal cancer (CRC) is still one of the main reasons for death from cancer worldwide. Xian Lian Jie Du decoction (XLJD) is based on Professor Zhou Zhongying\u2019s idea of \u201ctumour toxins\u201d, and it has shown some therapeutic effects in CRC; however, its active ingredients and specific molecular targets are not yet fully known. Active constituents of XLJD were screened from the TCMSP database (oral bioavailability \u226530%, drug-likeness \u22650.18). Predicted targets were cross-referenced with CRC-related genes from GeneCards, OMIM, and TTD, and a protein-protein interaction network was built to identify hub targets, which were then annotated using GO and KEGG enrichment. Quercetin, Kaempferol, Luteolin and some other compounds were chosen for molecular docking and 100-ns molecular dynamics simulations. LC-MS was used to identify the XLJD formulation, and then CCK-8 assays and RT-qPCR were carried out to determine the changes in gene expression in HT-29 cells. A total of 197 shared targets were found in XLJD and CRC. Topological evaluation shows that HIF1A, IL6, JUN, MMP9 and TNF are important genes, and most of them belong to the TNF, IL-17 and AGE-RAGE signalling pathways. All fifteen ligand-protein complexes had a docking energy below (more negative than) -5.0 kcal\/mol, and TNF was one of them; Molecular dynamics also showed that it had a good binding affinity and formed continuous hydrogen bonds and a stable low-energy state. LC-MS was used to identify the three kinds of compounds: quercetin, hesperidin and luteolin. A large amount of XLJD and every three flavonoids significantly reduced the mRNA expression of the five hub genes in HT-29 cells; however, the low-concentration group had little to no effect. In summary, XLJD and some of its main flavonoids may be targeting a group of CRC-related genes that are controlled by HIF1A, IL6, JUN, MMP9, TNF, etc. The above are the first transcriptional data; protein-based and\n                    <jats:italic>in vivo<\/jats:italic>\n                    verification will still be needed.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1882054","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:28:42Z","timestamp":1788150522000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Network pharmacology and experimental evidence of the anti-colorectal cancer potential of Xian Lian Jie Du formula: quercetin, kaempferol and luteolin jointly inhibit the HIF1A\/IL6\/TNF oncogenic pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Ning","family":"Du","sequence":"first","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ji","sequence":"additional","affiliation":[{"name":"Xinglin College of Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixing","family":"Liu","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqi","family":"Liu","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical 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