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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.

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Human respiratory syncytial virus (RSV) is a common virus that causes pneumonia and bronchitis, mostly in infants. Our previous study showed that Jinxin oral liquid (JOL), derived from traditional Chinese medicine, had anti-inflammatory and therapeutic effects on RSV-related pneumonia. However, little is known about the underlying mechanisms of these effects. During a viral infection, including RSV infection, the inflammasome pathway is excessively activated, resulting in an inflammatory reaction and severe tissue damage. Inhibition of the inflammasome pathway has shown good therapeutic effects on lung inflammation. In the present study, we explored the effect of JOL on RSV-induced excessive inflammation in BALB/c mice. Pathological evaluation of lung tissue and measurement of the lung index showed that JOL alleviated lung infection and tissue injury induced by RSV. The enzyme-linked immunosorbent assay showed that JOL reduced the release of inflammatory factors, including interleukin-1ß(IL-1ß), interleukin-18(IL-18) and interleukin-33(IL-33), in the serum and lung homogenate of RSV-infected mice. Furthermore, the results of real-time PCR, immunohistochemistry, and western blot analyses showed that JOL inhibited the immune inflammatory response of mice infected with RSV through blockade of the NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)/Caspase-1 signalling pathway, as evidenced by the down regulation of the mRNA and protein expression of three key components in the pathway. Collectively, our results showed that JOL inhibited pulmonary inflammation caused by RSV infection. Thus, JOL may be a promising remedy for lung inflammation caused by RSV infection and may help avoid lung tissue damage.

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Objective: To detect the relative abundance changes of metabolites in spleen to explore the antiviral effect of Jinxin Oral Liquid (JOL) against RSV pneumonia by GC-MS technology. Methods: BALB/c mice were challenged intranasally to establish the RSV pneumonia models and ig administered with JOL (27. 6 g·kg-1·d-1). After treated for 7 d, mice spleens were collected respectively. Metabolites were extracted by methanol, and then oximated, derevatized, and detected by GC-MS. Results: 35 metabolites in spleen were identified, among which L-proline, L-glutamic acid, valine, urea, hypoxanthine, glucose were statistically significant (P < 0.05). Conclusion: Anti-RSV infection of JOL may be associated closely with the regulation of immune function of mice spleen, and amino acid metabolism is involved.

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ETHNOPHARMACOLOGICAL RELEVANCE: Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). AIM OF THE STUDY: To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). MATERIALS AND METHODS: BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. RESULTS: JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. CONCLUSIONS: This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved.

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ETHNOPHARMACOLOGICAL RELEVANCE: Jinxin oral liquid (JOL) is used in traditional Chinese medicine (TCM) to treat influenza, cough, asthma, and viral pneumonia, on the basis of Ma Xing Shi Gan Tang (MXSGT) and the clinical experience of Professor Wang Shouchuan, one of the most prestigious pediatricians in China. AIM OF STUDY: To investigate the anti-inflammatory and antiviral activities of JOL in mice infected with respiratory syncytial virus (RSV). MATERIALS AND METHODS: Mice were orally administered JOL at doses of 27.6 g kg(-1) d(-1) and 55.2 g kg(-1) d(-1) for 1, 3, or 6d after RSV challenge. The viral loads in the lung tissue were measured by real-time RT-PCR. The levels of IFN-ß in bronchoalveolar lavage fluid (BLAF) and lung tissue were detected by ELISA and real-time RT-PCR, respectively. The mRNA and protein expression of TLR3, IRF3, and SOCS1 were detected by real-time RT-PCR and western blot, respectively. The protein expression of phoshorylated-IRF3 (p-IRF3) was detected by western blot. RESULTS: JOL significantly ameliorated lung inflammation in RSV-infected mice, and significantly reduced the viral load in the lung tissues. On days 2 and 4 after infection, the mRNA and protein expression of IFN-ß, TLR3, IRF3 (p-IRF3), and SOCS1 were significantly downregulated in RSV-infected mice treated with JOL. However, 7d after infection, JOL significantly upregulated the RSV-induced decrease in IFN-ß, TLR3, and IRF3 (p-IRF3), but reduced SOCS1 expression. CONCLUSIONS: JOL ameliorated lung inflammation and inhibited virus replication significantly in RSV-infected mice. During early stage infection, the effect of JOL was improved through inhibition of the TLR3-IRF3-IFN-ß signaling pathway and the expression of SOCS1, whereas during the later stage of infection, JOL upregulated the expression of key signaling molecules in the TLR3 signaling pathway and downregulated the expression of SOCS1.

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Objective: To study the effect of Jinxin Oral Liqiud medicated serum on RS virus virus (RSV) infected cell apoptosis and the regulation gene as Bcl-2, Bax on the different point in early time. Methods: Cell culture, serum pharmacology and Annexin V/PI technique combining with flow cytometry were used to detect cell apoptosis, Bcl-2 and Bax expression. Results: The total apoptosis rates of human embryonic lung fibroblast in JOL group in early time of 12h and 24h were significantly higher than that in RSV infected group (P