Molecular Mechanisms Associated With Amelioration Of Radiation Induced Gastrointestinal Mucositis By Compound Kushen Extracts

Abstract Radiation induced gastrointestinal mucositis (GIM) is a severe complication of radiotherapy that compromises patient quality of life and treatment efficacy. This study assessed the therapeutic potential and molecular mechanisms of two forms of herbal extracts, Compound Kushen Powder (CKP) and Compound Kushen Injection (CKI) in a rat model of GIM. Administration of either CKP or CKI to irradiated animals significantly reduced the severity of GIM symptoms. Transcriptomic analysis of jejunum and colon mucosa identified candidate mechanisms as well as common pathways between CKP and CKI. CKP modulated innate immune activation and inflammatory signalling, affecting genes such as Socs3 and Tlr4, while CKI promoted tissue repair and oxidative stress resistance through genes including Osm, Epha2, and Stat3. However, both forms of herbal extract enhanced stress response and stimulus regulation in our GIM model. These findings reveal common mechanisms shared by CKP and CKI that suppress symptoms of radiation induced GIM, along with extract specific effects on distinct pathways, acting on different set of genes. Competing Interest Statement The authors declare no conflict of interest as the experimental design, data analysis and conclusions were not influenced by Shanxi-Zhendong Pharmaceutical Co. Ltd. Footnotes Abbreviations: ANOVA, analysis of variance; CKI, Compound Kushen Injection; CKP, Compound Kushen Powder; CPM, counts per million; DE, differentially expressed; FDR, false discovery rate; GIM, gastrointestinal mucositis; GO, Gene Ontology; IL-1β, interleukin-1β; IL-6, interleukin-6; KEGG, Kyoto Encyclopedia of Genes and Genomes; MRNIP, MRN complex-interacting protein; NF-κB, nuclear factor kappa-B; ROS, reactive oxygen species; SD, standard deviation; SOCS3, Suppressor of cytokine signalling 3; TNF, tumour necrosis factor.