Network Pharmacology Analysis on the Mechanism of Xihuangwan in Treating Rectal Cancer and Radiation Enteritis

Abstract

Background: Recent studies have shown that XihuangWan (XHW) is a kind of Chinese medicine with significant anti-tumor and anti-inflammatory activities. However, its mechanism for preventing and treating radiation proctitis in rectal cancer patients during radiotherapy remains unclear. Methods: This study employed the network pharmacology to establish a “drug-active ingredient-target genedisease” network via using TCMSP, SymMap, GeneCard, and OMIM databases. The PPI network was conducted by the String tool. The core targets of XHW in the treatment of rectal cancer and radiation enteritis were identified by topological analysis, and the functional annotation analysis and pathway enrichment analysis were performed. Results: A total of 61 active ingredients of XHW ingredients, 4607 rectal cancer-related genes, 5803 radiation enteritis-related genes, and 68 common targets of XHW in the treatment of rectal cancer and radiation enteritis were obtained. PTGS1 and NR3C2, as identified potential targets, were significantly associated with OS of colorectal cancer patients. GO and KEGG enrichment analysis showed that bioinformatics annotation of these common genes is mainly involved in DNA-binding transcription factor, PI3K/Akt, TNF, HIF-1 signaling pathway, and colorectal cancer pathway. Conclusion: The active ingredients of XHW, mainly including Quercetin, Ellagic acid, and Stigmasterol, might act on common targets of rectal cancer and radiation enteritis, such as PTGS1, NR3C2, IL-6, EGFR, HIF-1A, CASP3, BCL2, ESR1, MYC, and PPARG, and regulate multiple signaling pathways like PI3K-Akt, TNF, and HIF-1 to inhibit tumor proliferation, tumor angiogenesis, inflammatory responses, and oxidative stress, thereby achieving prevention and treatment of radiation enteritis in rectal cancer patients during radiotherapy. It provided an important reference for further elucidating the anti-inflammation and anti-tumor mechanism and clinical application of XHW.