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INTRODUCTION

Head and neck tumors account for more than 6% of all cancers. The primary treatment for tumors of the head and neck is radiation therapy, which can induce oropharyngeal mucositis as a side effect. At present, there is no widely available therapeutic for the treatment of oropharyngeal mucositis in clinical practice. Based on the traditional prescription Liushen Wan, the pathogenesis and pathology, we developed a new Chinese medicine prescription and made Zhenhuang submicron emulsion (ZHSE) spray, which has an efficacious therapeutic effect for oropharyngeal mucositis. However, its mechanism is unclear.

METHODS

This research explored the mechanism behind the modulatory effects of ZHSE by a strategy of metabolomics and network pharmacology. Multivariate data analyses, including unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA), were performed. Potential biomarkers were identified depending on the mass-charge ratio of the selected compound. Statistical and pathway enrichment analysis was performed in the KEGG pathway database. Network pharmacology combining metabolomic analyses was conducted to illustrate the key targets and pathways.

RESULTS

Critical metabolic pathways were investigated, 56f biomarkers were enriched and key metabolites such as linoleic acid, 9,10-epoxyoctadecenoic acid, acetoacetic acid and citric acid were identified. A complex network of "compound-target-potential metabolite" interactions was drawn to illuminate the regulation of chemical constituents on key metabolites. These findings manifest that ZHSE regulates endogenous metabolite disorders during the treatment of oropharyngeal mucositis by various constituents, interacting with multiple targets associated with inflammation and pain.

CONCLUSION

In this work, we determined several critical biomarkers and metabolic pathways and identified the possible regulatory mechanism by which ZHSE functions in the treatment of oropharyngeal mucositis. This study provides a new perspective on integrating metabolomics and network pharmacology for exploring improved therapy for head and neck tumors based on the traditional classic prescription of LSW.

INTRODUCTION

METHODS

RESULTS

CONCLUSION

简介

头颈部肿瘤占所有癌症的 6%以上。头颈部肿瘤的主要治疗方法是放射治疗，这会导致口腔黏膜炎等副作用。目前，临床上还没有广泛用于治疗口腔黏膜炎的方法。基于传统方剂六神丸的发病机制和病理学，我们开发了一种新的中药方剂，并制成了正黄亚微米乳剂（ZHSE）喷雾剂，对口腔黏膜炎有疗效。然而，其机制尚不清楚。

方法

本研究采用代谢组学和网络药理学相结合的策略，探讨了 ZHSE 调节作用的机制。采用多变量数据分析，包括无监督主成分分析（PCA）和有监督正交偏最小二乘判别分析（OPLS-DA）。根据所选化合物的质荷比确定潜在的生物标志物。在 KEGG 途径数据库中进行统计和途径富集分析。通过网络药理学结合代谢组学分析，阐明关键靶点和途径。

结果

研究了关键代谢途径，富集了 56 个生物标志物，并鉴定了关键代谢物，如亚油酸、9,10-环氧十八烯酸、乙酰乙酸和柠檬酸。绘制了“化合物-靶标-潜在代谢物”相互作用的复杂网络，阐明了化学物质对关键代谢物的调节作用。这些发现表明，ZHSE 通过多种成分调节口腔黏膜炎治疗过程中的内源性代谢紊乱，与与炎症和疼痛相关的多个靶点相互作用。