Abstract
BACKGROUND: Aster tataricus, a perennial terrestrial herb with a rich history of use in traditional medicine, is renowned for its therapeutic properties. However, despite the widespread use of Aster tataricus, its antiviral efficacy and mode of action against viruses have not yet been studied. Here, we demonstrated that Aster tataricus extract (ATE) has antiviral effects and an underlying mechanism of action both in vitro and in vivo. METHODS: Antiviral effect of ATE was assessed against Influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus-1 (HSV) in RAW264.7 cells. Mechanism was explored by analyzing the induction of antiviral immune responses, including type-I interferon (IFN) signaling and cytokine secretion. In vivo, BALB/c mice were treated with ATE prior to infection with lethal influenza A subtypes, A/PR/8/34 (H1N1), A/Aquatic bird/Korea/W81/2005 (H5N2), and A/Chicken/Korea/116/2004 (H9N2). Survival rates, viral titers, and lung pathology were measured. High-performance liquid chromatography (HPLC) was used to identify active compounds in ATE, and their antiviral effects were further investigated. RESULTS: An effective dose of ATE significantly inhibited influenza A virus (PR8), NDV, and HSV replication in RAW264.7 cells. Mechanistically, we found that ATE induced an antiviral state, which includes upregulation of type-I interferon signaling and secretion of IFNs and pro-inflammatory cytokines in RAW264.7 cells. In vivo, ATE treatment showed increased survival due to reduced viral titers and less severe pathological changes in the lung, and the observed prophylactic effects were associated with increased secretion of IL-6, IFN-γ, and IFN-β in bronchoalveolar lavage fluid. Based on the reported information and HPLC analysis, quercetin, kaempferol, and ferulic acid were identified as active compounds in the aqueous fraction, and an effective dose of each compound exhibited antiviral effects similar to ATE against influenza viruses. CONCLUSIONS: These findings suggest that ATE and its active compounds act as immunomodulators and may be potential candidates as a source of promising natural antivirals for animals and humans.