Clinical Efficacy of Maxingshigantang Enema in Treating Infants with Pneumonia and Asthma and Intervention Mechanism of Lung-intestine Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Maxingshigantang enema in the treatment of infant viral pneumonia by comparing related indicators， and comprehensively evaluate the effect of traditional Chinese medicine （TCM） enema on the intestinal microenvironment. MethodSixty infants with viral pneumonia were selected and randomly divided into 3 groups. The dosage of enema drugs in high- （0.117 g·mL-1） and low-concentration （0.07 g·mL-1） TCM enema groups was same （3.5 g per time）， and the control group received normal saline enema， once a day for 7 days. Finally， the curative effect， total symptom score， salivary secretory immunoglobulin A （sIgA）， human beta defensin 2 （hBD2） and fecal calprotectin （CALP） of each group were statistically analyzed by SPSS 21.0， and the clinical efficacy of TCM enema in treating children with pneumonia and asthma was comprehensively evaluated. ResultThe curative effect of high-concentration TCM enema group （total effective rate 100%， χ2=7.059） was equivalent to that of low-concentration TCM enema group （total effective rate 95%， χ2=4.329）， higher than that of control group （total effective rate 70%） （P<0.017）. After treatment， compared with control group and low-concentration TCM enema group， high-concentration TCM enema group had higher total symptom score of children （P<0.05， P<0.01）. The proportion of coccobacillus was reduced in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The salivary sIgA concentration was increased in three groups （P<0.05）， with high-concentration TCM enema group higher than the other groups （P<0.01）. The hBD2 concentration was decreased in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The three groups reduced the fecal CALP concentration， and high-concentration TCM enema group had the highest reduction， followed by low-concentration TCM enema group （P<0.01）. ConclusionTCM enema outweighs western medicine in improving clinical symptoms， intestinal flora， and mucosal immune function， and reducing inflammation in children， and the high-concentration TCM enema group has better curative effect. Therefore， with easiness to operate， high compliance， and significant therapeutic effect， TCM enema is worthy of clinical promotion.

The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin.

ETHNOPHARMACOLOGICAL RELEVANCE: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia. AIM OF THE STUDY: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated. MATERIALS AND METHODS: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs. RESULTS: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo. CONCLUSION: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.

A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry.

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.

Chromatographic isolation of nanoparticles from Ma-Xing-Shi-Gan-Tang decoction and their characterization.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal decoction is a complex dispersion system containing solutes, colloid, aggregates, emulsions and precipitates. In which phase bioactive phytochemicals are dispersed determines their delivery, action and metabolism. This study took ephedrine, a well-studied and widely used phytochemical, as an example to elucidate its exact distribution in the phases of Ma-Xing-Shi-Gan-Tang decoction (MXSGT), which is an Ephedra sinica Stapf. containing traditional Chinese medicinal formula, and the biological meaning of this distribution correspondingly. It may provide an important update to the safety and efficacy assessment of the herbal decoction and its active phytochemicals. MATERIALS AND METHODS: In this study, the decoction was fractionated with size-exclusion chromatography coupled with multi-angle laser light scattering detector. The morphology of fractionated nanoparticles was observed with AFM and SEM. The bioactivities of the decoction, the ephedrine alkaloids loaded NPs (prepared by chromatography isolation) and the synthetic ephedrine were assessed by cell proliferation tests using five cell lines, namely Caco-2, L-02, Hep-G2, NR-8383, and Hela-229. RESULTS: Nanoparticles with radii of gyration ranged from 50 to 150 nm were isolated, in spherical shape. Further analysis of nanoparticles on the subsequent reversed phase chromatography revealed that the majority of ephedrine (99.7%) and pseudoephedrine (95.5%) were associated with these nanoparticles, rather than dispersed freely in the real solution. The addition of both the herbal decoction and the separated ephedrine-loaded nanoparticles reserved higher cell viability/proliferation than that of the sole synthetic ephedrine among the Caco-2, L-02, Hep-G2, and NR-8383 cells. In contrast, the nanoparticles reduced the proliferating power of ephedrine on Hela-229 cells. In general, the ephedrine-loaded NPs conducted the intermediate influences on the cell viability, in either way. CONCLUSIONS: The colloidal nanoparticles were separated from the decoction. The association of ephedrine alkaloids with nanoparticles was demonstrated and may have changed the bioactivity of the alkaloids. The naturally occurred colloidal nanoparticles may play an important role in the pharmacological properties of both the decoction and its active phytochemicals, therefore warrant further studies.