Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Engineering Laboratory for Digital Telemedicine Service, The first Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Chin J Nat Med. 2021 Dec;19(12):930-943. doi: 10.1016/S1875-5364(22)60150-X.
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·d. 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. 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, 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.
口腔黏膜炎（OM）是头颈部肿瘤放疗最常见的不良反应。在严重的情况下，它可能导致治疗中断，从而影响疾病的控制和生活质量。双花百合片（SBT）是一种中药配方，在中国用于治疗 OM。它已经有 30 多年的临床疗效，但具体机制尚不完全清楚。随着多种组学的发展，探索中药复方的作用机制成为可能。基于转录组学和代谢组学，我们探索了 SBT 治疗 OM 的作用机制。采用 5-FU 诱导建立 OM 大鼠模型，分别给予 SBT 剂量为 0.75 和 3 g·kg·d。为了寻找 SBT 的作用靶点和相关代谢物，通过转录组学和代谢组学检测失调基因和代谢物。采用 ELISA 检测白细胞介素-17（IL-17）和肿瘤坏死因子-α（TNF-α）等免疫相关指标。通过流式细胞术分析 Treg 细胞紊乱。结果表明，SBT 能明显缓解 OM 大鼠症状和溃疡组织的炎症浸润。SBT 给药后，包括亚油酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成在内的炎症相关代谢途径明显改变。此外，SBT 给药后促炎因子如 IL-17 和 TNF-α的产生也显著减少。此外，SBT 给药可显著改善 OM 造模大鼠脾脏中 Treg 细胞的浸润程度，从而维持机体的免疫平衡。本研究表明，SBT 调节亚油酸代谢、甘油磷脂代谢和氨基酸代谢，抑制 IL-17/TNF 信号转导，恢复 OM 大鼠 Treg 和 Th17 细胞的平衡，从而缓解化疗引起的 OM。
