Abstract
Background: Oral mucositis (OM) caused by chemotherapy is the most common complication in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which can affect the control of the disease and the life quality of patients. Shuanghua Baihe tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but its mechanism is still unclear. With the rise of multiple omics, it is possible to study the mechanism of Chinese herbal compound prescriptions. Methods: Based on transcriptomics and metabolomics, we explored the mechanism of SBT in the treatment of OM. The OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3g/kg/day. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Results: Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, was also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM model rats was significantly improved by SBT administration, thus maintaining the immune balance of the body.Conclusions: This study shows that SBT regulates inoleic acid metabolism, Glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.