Journal
CHINESE JOURNAL OF NATURAL MEDICINES
Volume 19, Issue 12, Pages 930-943Publisher
CHINESE JOURNAL NATURAL MEDICINES
DOI: 10.1016/S1875-5364(22)60150-X
Keywords
Oral mucositis; Shuanghua Baihe tablet; Transcriptomics; Metabolomics; IL-17/TNF signal pathway
Funding
- Clinical Research Special Fund of Wu Jieping Medical Foundation [320.6750.2020-04-9]
- National Key Research and Development Program of China [2017YFC0909900]
- National Natural Science Foundation of China [82002433]
- Science and Technology Project of Henan Provincial Department of Education [18A320044, 21A320036]
- Henan Province Medical Science and Technology Research Project Joint Construction Project [LHGJ20190003, LHGJ20190055]
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This study explored the underlying mechanism of Shuanghua Baihe Tablet (SBT) in the treatment of oral mucositis (OM) using transcriptomics and metabolomics. The results showed that SBT significantly alleviated symptoms of OM in rats, reduced inflammatory related metabolic pathways, and inhibited IL-17/TNF signal transduction to restore Treg and Th17 cell balance.
Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. 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 the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g.kg(-1).d(-1) . 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-alpha (TNF-alpha) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. 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-alpha, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates 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.
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