Yingjie Gao

Astragaloside IV exerts antiviral effects against coxsackievirus B3 by upregulating interferon-γ

Coxsackievirus B3 (CVB3) is a major pathogen for viral myocarditis and dilated cardiomyopathy in children and young adults. The aim of this study was to determine the antiviral effects of astragaloside IV against CVB3, and the underlying mechanism. First, we evaluated antiviral effects of astragaloside IV in vitro by measuring the virus titers of CVB3 in primarily cultured myocardial cells infected with CVB3, and in vivo by assessing the morbidity, mortality, heart-to-body weight ratio (HW/BW), and virus titers in BALB/c mice infected with CVB3. Then, we performed serum pharmacological experiments by testing the effect of sera from SD rats treated with astragaloside IV on proliferation of CVB3 in primarily cultured myocardial cells. Finally, we determined the effect of astragaloside IV on IFN-γ mRNA expression in the hearts of infected BALB/c mice. We observed that astragaloside IV decreased virus titers of CVB3 in primarily cultured myocardial cells. Morbidity, mortality, HW/BW, and virus titers all decreased, and necrosis and mononuclear cell infiltration were alleviated in CVB3-infected mice treated with astragaloside IV, compared with those infected mice without the treatment. In addition, proliferation of CVB3 was inhibited by the sera of rats treated with astragaloside IV. Moreover, we observed that IFN-γ mRNA expression was increased in mice treated with astragaloside IV. Therefore, we conclude that astragaloside IV exerts antiviral effects against CVB3 by upregulating expression of IFN-γ mRNA.

Evaluation of pharmacodynamic activities of EPs® 7630, a special extract from roots of Pelargonium sidoides, in animals models of cough, secretolytic activity and acute bronchitis

Abstract Background EPs® 7630 is a proprietary aqueous-ethanolic extract from roots of Pelargonium sidoides DC and has been demonstrated to dispose among others of antibacterial, antiviral, immunomodulatory, antioxidant, and tissue-protective activity. It is an approved medicinal product in more than 50 countries for the treatment of airway infections such as acute bronchitis, common cold, and sinusitis. Purpose While the pharmacological effects of EPs® 7630 have extensively been evaluated in diverse in vitro test systems, the number of publications reporting results from in vivo models is limited. Study design In the present study antitussive, secretolytic, and anti-inflammatory effects of EPs® 7630 were assessed in animal experiments following oral administration at human equivalent doses. Methods Antitussive effects were evaluated using ammonia- and citric acid-induced models of cough in mice (20, 40, 120 mg/kg) and guinea pigs (10, 20, 45 mg/kg), respectively. For the determination of secretolytic activity tracheobronchial secretion of intraperitoneally injected phenol red was determined in mice, while antiinflammatory action was assessed in an acute bacterial bronchitis model in rats. Results A significant and dose-dependent reduction of cough frequency was observed in both cough models, which was accompanied by a prolongation of cough latency time. Similarly, the extract exerted a marked secretolytic activity in mice. Induction of acute bacterial bronchitis caused characteristic histopathological changes in lung tissue adjacent to trachea and bronchi. The degree of these lesions was significantly reduced in rats treated with EPs® 7630 at doses of 30 and 60 mg/kg. This protective effect at least partially seems to be mediated by an up-regulation of superoxide dismutase and a subsequent protective effect against oxidative stress as indicated by a reduced serum level of malondialdehyde. Conclusion The present data further support the therapeutic use of EPs® 7630 in respiratory tract infections and provide a basis for detailed studies on its bioactive constituents as well as their in vivo mode of action.

The inhibitory effect of iridoid glycoside extracted from Fructus Gardeniae on intracellular acidification and extracellular Ca2+ influx induced by influenza A virus.

Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. Iridoid glycoside is one of the main active components from Fructus Gardeniae with antivirus and anti-inflammatory characteristics. The present study was designed to investigate the inhibitory effect of iridoid glycoside extracted from Fructus Gardeniae (IGE) on influenza and explore the potential mechanism of the action. In vitro, IGE exhibited highest activity against influenza virus A/FM1/47 induced visible cytopathic effect (CPE), with half maximal inhibitory concentration and therapeutic index values of 3.15 mg/mL and 11.37, respectively, and the replication of influenza virus A/FM1/47 was inhibited markedly by IGE at the concentrations of 25, 12.5 and 6.25 mg/mL. In vivo, treatment of mice with IGE decreased pulmonary index, viral titers and M2 protein expression in a dose-dependent manner. IGE increased the declining pHi induced by influenza virus significantly at the concentrations of 25 and 12.5 mg/mL 0.5 or 1 h post-infection, respectively. IGE treatment inhibited elevation of [Ca2+]i significantly at the concentrations of 25 and 12.5 mg/mL 0.5, 1 or 24 h post-infection, respectively. In addition, IGE reduced the rate of early-apoptotic cells at the concentrations of 25, 12.5 and 6.25 mg/mL, but showed no apparent effect on the rate of late-apoptotic cells. Our study demonstrates that IGE possesses antiviral activity against influenza A virus, and the antiviral action might be related to the inhibition of intracellular acidification and Ca2+ influx during fusion and uncoating of influenza replication cycle.

Antiviral activity of Jinchai capsule against influenza virus

Abstract Objective To evaluate the effect on influenza virus of Jinchai, a capsule made of Traditional Chinese Medicine. Methods Madin-darby canine kidney (MDCK) cells were infected with the FM1 strain of influenza virus A (subtype H1N1) in vitro. They were used to explore how Jinchai affected cell adsorption, cell membrane fusion, transcription and replication of the influenza virus. Hemagglutinin (HA) protein, intracellular pH, and influenza virus protein acid (PA) polymerase subunit were detected with confocal microscopy and real-time fluorescent quantitative polymerase chain reaction. Results Jinchai significantly reduced the expression of HA and PA polymerase subunit mRNA in infected MDCK cells. Jinchai also significantly decreased intracellular pH in infected cells. Conclusions Jinchai had strong anti-influenza activity against the influenza virus. It weakened the ability of the influenza virus to adsorb to cell wall and fuse with cell membranes in the early infection stage, and inhibited the transcription and replication of the virus.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Effect of Shufeng Jiedu capsules as a broad-spectrum antibacterial

This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings.

Ameliorative Effects of Infantile Feire Kechuan Oral Solution on Mycoplasma Pneumoniae Pneumonia in Infant Mouse and Rat Models

Mycoplasma pneumoniae (MP) infection is a major pathogen of community-acquired pneumonia (CAP) in children worldwide. Infantile Feire Kechuan Oral Solution (IFKOS) has been used for the treatment of MP pneumonia clinically in China for many years. The present study was designed to investigate the therapeutic effect of IFKOS on MP pneumonia and explore the potential mechanism of the actions. The infant BALB/c mouse and Wistar rat models of MP infection were successfully established to confirm the therapeutic effects of IFKOS, followed by assays for related cytokines and investigations of the IgM response involved. The results showed that IFKOS exhibited an inhibitory effect on pulmonary index (PI) and effectively reduced the degree of lesions in the lungs. The lethal rate of mice was significantly decreased while survival time of mice was dramatically increased by IFKOS treatment in comparison to infection control, respectively. IFKOS treatment (40, 20, and 10ml/kg) significantly decreased the level of MP-IgM in a dose-dependent manner, whereas IFKOS showed no obvious inhibitory effect on the increase of relative expression of MP-DNA. In addition, the elevated IL-2 and TNF-α levels were significantly reduced and the decreased IL-6 level was significantly enhanced by IFKOS treatment. Our study demonstrates that IFKOS has inhibitory effect on MP infection in infant mouse and rat models of MP pneumonia and protective effect from lethal MP challenge in infant murine model. These anti-MP effects might be related to suppression of the IgM response and a reversal the imbalance of Th1/Th2 cytokines induced by MP infection.

Antitumor Effect of Zhihuang Fuzheng Soft Capsules on Tumor-Bearing Mice

Chinese medicines (CMs) have been shown to have some advantages in preventing and controlling tumors. In this study, we investigated the antitumor effect of ZFSC by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group, and the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group and showed a good dose-response relationship. There was no significant effect on human colon cancer, although inhibition trends disappeared in the bar chart. In order to verify the immunomodulatory effect of ZFSC, ELISA was used to analyze serums IL-2, TNF-α, and IFN in spleens. The results showed that ZFSC could enhance the immune function of tumor-bearing mice. ZFSC reduced IFN-γ and TNF-α content in the serum of HT-1080 tumor-bearing mice and inhibit PD1 and PDL1 and suggested that the antitumor mechanism of ZFSC on human fibrosarcoma could be attributed to inhibition of the PDL1/PD1 pathway.