Drug Design, Development and Therapy (Sep 2022)
Metabolomics Combined with Network Pharmacology-Based Strategy to Reveal the Underlying Mechanism of Zhenhuang Submicron Emulsion in Treating Oropharyngeal Mucositis Complications of Radiation Therapy for Head and Neck Cancer
Abstract
Wei Chen,1,* Chunyu Li,1,* Dujia Jin,2 Yafei Shi,1 Mingyu Zhang,1 Mingming Bo,1 Di Qian,1 Mengyang Wang,1 Guohui Li1 1Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guohui Li, Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Tel +861087788573, Email [email protected]: 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.Keywords: metabolomics, network pharmacology, mucositis, traditional Chinese medicine, head and neck tumors
