Brain Metabolomics Reveal the Antipyretic Effects of Jinxin Oral Liquid in Young Rats by Using Gas Chromatography⁻Mass Spectrometry.

Pyrexia is considered as a part of host's defense response to the invasion of microorganisms or inanimate matter recognized as pathogenic or alien, which frequently occurs in children. Jinxin oral liquid (JXOL) is a traditional Chinese medicine formula that has been widely used to treat febrile children in China. Experimental fever was induced by injecting yeast into young male Sprague-Dawley rats (80 ± 20 g) and the rectal temperature subsequently changed. Four hours later, the excessive production of interleukin (IL)-1ß and prostaglandin (PG) E2 induced by yeast was regulated to normal by JXOL administration. A rat brain metabolomics investigation of pyrexia of yeast and antipyretic effect of JXOL was performed using gas chromatography-mass spectrometry (GC-MS). Clear separation was achieved between the model and normal group. Twenty-two significantly altered metabolites were found in pyretic rats as potential biomarkers of fever. Twelve metabolites, significantly adjusted by JXOL to help relieve pyrexia, were selected out as biomarkers of antipyretic mechanism of JXOL, which were involved in glycolysis, purine metabolism, tryptophan mechanism, etc. In conclusion, the brain metabolomics revealed potential biomarkers in the JXOL antipyretic process and the associated pathways, which may aid in advanced understanding of fever and therapeutic mechanism of JXOL.

Gas chromatography-mass spectrometry based plasma metabolomics of H1N1-induced inflammation in mice and intervention with Flos Lonicerae Japonica-Fructus Forsythiae herb pair.

Flos Lonicerae Japonica-Fructus Forsythiae herb pair (Yin-Qiao in Chinese, YQ), is used clinically for the treatment of viral pneumonia due to its heat-clearing and detoxifying functions. In the present work, the effect of YQ in H1N1-induced inflammation in mice was investigated by metabolomics based on GC-MS. Body weight and histological results were used to assess the lung injury, while the levels of IL-6 and TNF-α in plasma were used to evaluate the extent of inflammation. The acquired GC-MS data were further subjected to multivariate data analysis, and the significantly altered metabolites identified. After statistical and pathway analysis, 17 significantly altered metabolites and 3 possible metabolic pathways were found in plasma between normal and H1N1-induced pneumonia mice, while 17 significant differential metabolites were identified when YQ treatment group was compared with model group. This work indicates that oral administration of YQ could protect mice from H1N1-induced inflammation partially by ameliorating the associated metabolic disturbances.

A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced Arthritis Rats.

A sensitive and rapid ultra high-performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin, daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active components in Zushima-Gancao extract. The analytes and internal standard (IS) were separated in a Hypersil Gold C18 column and detected on a triple-stage quadrupole mass spectrometer using the validated method. All analytes exhibited good linearities (R² > 0.98), and the lower limit of quantification (LLOQs) were sufficient for quantitative analysis. Intra- and inter-batch precision were all within 14.96% while the accuracy of nine analytes ranged from -17.99 to 14.48%, and these results were all within acceptance criteria. The extraction recoveries, matrix effects, and stabilities were all satisfactory. Main pharmacokinetic parameters of each compound were compared, and significant differences were found in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last one, between the two groups. Therefore, adjuvant-induced arthritis has different effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The comparative pharmacokinetic study between normal and adjuvant-induced arthritis rats might provide more comprehensive information to guide the clinical usage of Zushima-Gancao extract for treating RA.