Integrating Metabolomics and Network Pharmacology to Explore the Protective Effect of Ginsenoside Re against Radiotherapy Injury in Mice.

Ionizing radiation (IR) can cause radiation damage, mutagenesis, or carcinogenesis in the irradiated subject. It is manifested as metabolic disorders of the body and damage to the immune system, nervous system, and endocrine system, which can lead to physiological and pathological changes and endogenous metabolic disorders. Ginsenoside Re (G-Re), a single component of traditional Chinese medicine, has a certain ameliorating effect on radiation damage. However, its mechanism of action in the treatment of radiotherapy injury remains unclear. With this purpose, the hematopoietic function of mice damaged by X-ray radiation was studied, and the protective effect of G-Re on mice damaged by radiation was preliminarily evaluated. Network pharmacology and metabolomics analysis are used to further reveal the mechanism of G-Re to improve radiation damage through metabolomics research. Results of metabolomics analysis showed that 16 potential biomarkers were identified as participating in the therapeutic effect of G-Re on IR. Most of these metabolites are adjusted to recover after G-Re treatment. The pathways involved included glycerophospholipid metabolism, sphingolipid metabolism, and linoleic acid metabolism. According to network pharmacology analysis, we found 10 hub genes, which is partly consistent with the findings of metabolomics. Further comprehensive analysis focused on 4 key targets, including SRC, EGFR, AKT1, and MAPK8, and their related core metabolites and pathways. This study combines metabolomics and network pharmacology analysis to explore the key targets and mechanisms of G-Re in the treatment of IR, in order to provide new strategies for clinical treatment of radiotherapy injury.

UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum Polysaccharide (GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. THE AIM OF THE STUDY: This study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: Thirty mice were randomly divided into three groups,and namely 10 per group. The normal control group and the radiation model with normal saline and GLP group with GLP treatment (96 mg·kg-1) for 14 days. 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. RESULTS: The number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. CONCLUSION: GLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice.