4(3H)-Quinazolone regulates innate immune signaling upon respiratory syncytial virus infection by moderately inhibiting the RIG-1 pathway in RAW264.7 cell.

The root of Isatis indigotica, also known as Ban-Lan-Gen (BLG), is commonly used for prevention and early treatment of respiratory virus infection, but the underlying mechanisms of action remain unclear. In the early stage of infection, the innate immune system is activated by virus, and related immune cells such as macrophages secrete large amounts of cytokines including IFNs and ILs. On the one hand, these cytokines can remove virus. On the other hand, they dominantly mediate the inflammatory injury caused by viral infection. This study evaluated the effects of the main active plasma components of BLG (tryptanthrin B, 4(3H)-Quinazolone and epigoitrin) on the innate immune response of respiratory syncytial virus (RSV)-activated mouse macrophages. ELISA, real-time PCR and reporter gene assay all showed that 4(3H)-Quinazolone inhibited RSV-induced IFN-ß secretion in mouse macrophages in a dose-dependent manner within a concentration range (0.3125-1.25µM) having no effects on cell viability, but the inhibitory effects were inferior to those of ribavirin. Western blot analyses further revealed that 4(3H)-Quinazolone inhibited RSV-induced expression of RIG-I (Retinoic acid-Inducible Gene-I) in mouse macrophages dose-dependently, thereby suppressing the transcription of IFN-ß, with lower effects than those of ribavirin. This may be one of the important mechanisms by which BLG inhibited inflammatory injury without affecting the immune system to eliminate virus. The results inspire future studies to elucidate the antiviral mechanisms of traditional Chinese medicine drugs.

Immune responses to foot-and-mouth disease DNA vaccines can be enhanced by coinjection with the Isatis indigotica extract.

The Isatis indigotica extract is widely used in clinical practice for the treatment of influenza, epidemic hepatitis, epidemic encephalitis B etc. The goal of this study was to investigate whether coinjection of the Isatis indigotica extract with foot-and-mouth disease virus (FMDV) DNA vaccine could increase the protective immune response. Mice were vaccinated twice with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone. Compared with the group of DNA vaccine alone, in the group that received DNA vaccine plus the Isatis indigotica extract was observed a significant increase in not only FMDV-specific antibody response but also T cell proliferation assay. All swine immunized with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone were partially protected from FMDV challenge, but the signs of DNA vaccine plus the Isatis indigotica extract group were less severe than that of DNA vaccine alone. Coinjection of the Isatis indigotica extract with DNA vaccine has adjuvant effect on the immune response against viral pathogens and its application provides an effective strategy to improve the efficacy of DNA vaccines.