RESUMEN
Yinhuapinggan granule (YHPG), a Chinese medicine granule based on Ma-Huang-Tang (Ephedra Decoction) and the clinical experience of Professor Wan Haitong, is used in traditional Chinese medicine (TCM) for the treatment of colds, influenza, fever, inflammation and cough. This study investigated the antiviral effects of YHPG on the production of inflammatory cytokines in influenza virus (IFV)-infected mice and evaluated the effect of YHPG on the expression of NF-κB p65 and the level of key signaling molecules in the TLR4 signaling pathway. ICR mice were orally administrated YHPG at doses of 7.5, 15 and 30 g kg(-1) day(-1) for 2 or 6 days after IFV infection. On days 3 and 7 after infection, YHPG (15 g/kg and 30 g/kg) significantly increased levels of interleukin (IL)-2 and interferon gamma and decreased levels of IL-4, IL-5 and tumor necrosis factor (TNF) in serum compared with the IFV control group. Furthermore, the expression of TLR4, MyD88, TRAF6 and NF-κB p65 at the mRNA and protein level was significantly lower in the YHPG (15 and 30 g/kg) treatment groups than in the IFV control group. These results suggest that YHPG has antiviral effects in IFV-infected mice, which is associated with the inhibition of the TLR4-MyD88-TRAF6 signaling pathway and the expression of NF-κB p65.
Asunto(s)
Antivirales/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Ephedra/metabolismo , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Ephedra sinica , Femenino , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Interleucina-4/genética , Interleucina-5/sangre , Masculino , Ratones , Ratones Endogámicos ICR , Factor 88 de Diferenciación Mieloide/genética , Preparaciones de Plantas/farmacología , ARN Mensajero/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Transcripción ReIA/biosíntesis , Factor de Transcripción ReIA/genética , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Yinhuapinggan granule (YHPG), a Chinese medicine granule on the basis of Ma-Huang-Tang (Ephedra Decoction) and the clinical experience of Professor Wan Haitong, has been shown to inhibit the growth of influenza virus in vitro. The aim of this study was to investigate the protective effects of YHPG on mice with influenza viral pneumonia and its effects on regulating related inflammatory cytokines in influenza virus A-infected mice. ICR mice were inoculated intranasally with 15 LD50 viral dose of influenza virus A/PR/8/34 (H1N1) and treatments with YHPG (7.5, 15 and 30g/kg) were orally administrated daily for 5 consecutive days after challenge, respectively. The results showed that mortality rate, lung index, lung histopathological changes, IL-6 and TNF-α in serum were significantly attenuated in the treatment of YHPG (15 and 30g/kg) than those in the IFV control group, while the levels of IL-2 was significantly enhanced. Moreover, the RT-PCR results revealed that YHPG (15 and 30g/kg) significantly depressed the expressions of IL-1ß, IFN-γ and TNF-α mRNA in lung tissues. Furthermore, the immunohistochemical staining results also revealed that the expression of NF-κB p65 proteins was downregulated when treated with YHPG (15 and 30g/kg). These results showed YHPG has protective effects on IFV-infected mice, due to its ability of alleviation of lung damage, regulation of the cytokine production via inhibiting the NF-κB p65 activation, attenuation of systemic and pulmonary inflammatory responses.
Asunto(s)
Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Virus de la Influenza A/inmunología , Pulmón/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Neumonía Viral/prevención & control , Animales , Citocinas/genética , Citocinas/metabolismo , Pulmón/inmunología , Pulmón/virología , Masculino , Medicina Tradicional China , Ratones , Ratones Endogámicos ICR , FN-kappa B/genética , FN-kappa B/metabolismo , Infecciones por Orthomyxoviridae/complicaciones , Neumonía Viral/etiologíaRESUMEN
To study the effect of Yinghua Pinggan granule (YHPG) against influenza A/H1N1 virus in vivo and on the immunologic function of infected mice. The intranasal influenza virus infection was adopted in ICR mouse to establish the influenza virus pneumonia model. At the 3rd and 7th day after the infection, the lung index and pathologic changes in lung tissues of mice were detected. Realtime PCR and flow cytometry were employed to observe the virus load in lung tissues and the levels of CD4+, CD8+, and CD4+/CD8+ in peripheral blood. The result showed that at the 3rd and 7th day after the infection, YHPG (15, 30 g x kg(-1)) can significant decrease in the lung index and virus load in lung tissues of mice infected with influenza virus, alleviate the pathologic changes in lung tissues, significantly increase the levels of CD4+ and CD4+/CD8+ ratio and reduce the levels of CD8+ in whole blood. This indicated that YHPG can inhibit the influenza virus replication, alleviate pulmonary damage and adjust the weak immunologic function of infected mice, with a certain therapeutic effect on mice infected by H1N1 virus in vivo.