ABSTRACT
Ge Gen Decoction (GGD), a Traditional Chinese Medicine prescription, is mainly used to treat infectious respiratory diseases and can relieve the symptoms of influenza A virus (IAV) infection. However, the underlying mechanism of GGD against IAV infection remains unclear. In this study, we found that GGD had moderate anti-IAV activity in vitro. GGD was more effective when given before the viral infection and targeted the viral attachment and replication stages rather than the internalization stage. In vivo, GGD treatment reduced thevirus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes in H1N1-infected mice. We observed the changes in several key immuno-related indexes in GGD administrated H1N1-infected mice with anti-IAV drug oseltamivir phosphate as the control. GGD treatment decreased the expression of TNF-α and improved Th1/Th2 immune balance to reduce the excessive immune response in H1N1-infected mice. Besides, the expression of the toll-like receptor 7 signaling pathway in H1N1-infected mice decreased after GGD treatment. Our results showed that GGD has anti-IAV activity and can modulate the immune system to relieve lung inflammation.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Influenza A virus/drug effects , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/immunology , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cytokines/metabolism , Dogs , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Female , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/physiology , Influenza A virus/physiology , Lung/drug effects , Lung/immunology , Lung/pathology , Lung/virology , Madin Darby Canine Kidney Cells , Membrane Glycoproteins/metabolism , Mice, Inbred ICR , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Oseltamivir/administration & dosage , Oseltamivir/pharmacology , Oseltamivir/therapeutic use , Signal Transduction/drug effects , Th1-Th2 Balance/drug effects , Toll-Like Receptor 7/metabolism , Virus Attachment/drug effects , Virus Replication/drug effectsABSTRACT
Emerging viruses such as Ebola virus (EBOV), Lassa virus (LASV), and avian influenza virus H5N1 (AIV) are global health concerns. Since there is very limited options (either vaccine or specific therapy) approved for humans against these viruses, there is an urgent need to develop prophylactic and therapeutic treatments. Previously we reported a high-throughput screening (HTS) protocol to identify entry inhibitors for three highly pathogenic viruses (EBOV, LASV, and AIV) using a human immunodeficiency virus-based pseudotyping platform which allows us to perform the screening in a BSL-2 facility. In this report, we have adopted this screening protocol to evaluate traditional Chinese Medicines (TCMs) in an effort to discover entry inhibitors against these viruses. Here we show that extracts of the following Chinese medicinal herbs exhibit potent anti-Ebola viral activities: Gardenia jasminoides Ellis, Citrus aurantium L., Viola yedoensis Makino, Prunella vulgaris L., Coix lacryma-jobi L. var. mayuen (Roman.) Stapf, Pinellia ternata (Thunb.) Breit., and Morus alba L. This study represents a proof-of-principle investigation supporting the suitability of this assay for rapid screening TCMs and identifying putative entry inhibitors for these viruses. J. Med. Virol. 89:908-916, 2017. © 2016 Wiley Periodicals, Inc.