ABSTRACT
OBJECTIVE: To analyze the endogenous metabolite changes in the sera of kidney-yang deficiency syndrome mice infected with influenza virus A after intervention by ribavirin. And to explore the mechanism of pharmacological or toxicity effect of ribavirin. METHODS: KM mice were randomly divided into three groups as normal group, model group and ribavirin group. Mice were infected with virus A after fifteen days Kidney-Yang deficiency syndrome was established. Ribavirin group were orally administrated with ribavirin for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature were recorded daily. Serum samples were collected from mouse 24 h after the last administration for HPLC-TOF/MS analysis. RESULTS: The results show that ribavirin has good therapeutic effects on the lung index and high mortality rate of mice model. Compared with normal and model groups, the body weight and rectal temperature of them performed falling continuously. The LC-MS data were analyzed with multivariate statistical analysis and 14 potential metabolic markers were obtained which contained D-glucose, sphinganine, linoleic acid and so on. In ribavirin group, metabolism of linoleic acid, arachidonic acid and sphinganine appeared the trend of normal. And sugar and glycerophospholipid became disorders. CONCLUSION: The metabolomics study and pharmacological experiment show that ribavirin might play a role of efficacy in a way that has close correlation with the linoleic acid, arachidonic acid and sphingolipid metabolic pathways. And the toxicity effect may be related to sugar and glycerophospholipid metabolic pathways.
ABSTRACT
This study aimed to analyze the endogenous metabolite changes in the serum of mice infected with H1N1 virus after intervention by Mahuang-Xixin-Fuzi decoction (MXF) based on metabolomics method, investigate potential biomarkers and related metabolic pathways, and explore the therapeutic mechanism of MXF through metabolomics technology. Thirty-six Kunming (KM) mice were randomly divided into three groups: normal group, model group and MXF group. Influenza virus H1N1 was used by nasal drip to establish influenza mice model. The mice in MXF group were orally administrated with MXF for 6 consecutive days after inoculation, and the other two groups were given with equal volume of saline solution in the same way. Body weight, rectal temperature, morbidity and mortality were recorded daily. Serum samples were collected 24 hours after the last administration for HPLC-TOF-MS analysis. The results showed that as compared with the normal group, the body weight and rectal temperature were decreased in model group, and their lung index and mortality rate were significantly increased (P<0.05); MXF had good therapeutic effects on the abnormity of body weight, rectal temperature, lung index and high mortality rate of mice infected with H1N1 virus. The original data collected from the serum samples were analyzed with R language, MPP, SIMCA-P and other software, and significant changes were found in 14 kinds of endogenous substances from mice serum (P<0.05). As compared with model group, the potential metabolic markers in MXF group recovered to normal levels to a certain degree after being intervened by MXF. Further analysis with MetPA data platform showed that, the pathways involved in 14 metabolites included glucose metabolism, arachidonic acid metabolism, glycerophospholipids and sphingolipids metabolism etc. The metabolomics study and pharmacological experiment showed that MXF might play a role of efficacy by improving glucose metabolism, regulating arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolic pathways.