An active component containing pterodontic acid and pterodondiol isolated from Laggera pterodonta inhibits influenza A virus infection through the TLR7/MyD88/TRAF6/NF‑κB signaling pathway

Abstract

The influenza virus is a pathogen that can cause pandemic and epidemic outbreaks, and therefore represents a severe threat to human health. Antiviral drugs have an important role in the prevention and treatment of influenza, although the increasing emergence of drug resistance has given rise to a requirement for the development of novel antiviral drugs. In the present study, an active component (C8) isolated from Laggera pterodonta was evaluated. The nuclear magnetic resonance spectroscopy and mass spectrometry analysis results revealed that two eudesmane‑type sesquiterpene compounds were identified in C8; pterodontic acid and pterodondiol. C8 was demonstrated to have a broad‑spectrum effect against different influenza viruses, including human and avian influenza viruses, with a half maximal inhibitory concentration value of 19.9‑91.4 µg/ml. The antiviral mechanisms of C8 were further clarified. Western blot analysis verified that C8 inhibited Toll‑like receptor 7, myeloid differentiation primary response protein 88 and tumor necrosis factor (TNF) receptor associated factor 6 expression, in addition to p65 phosphorylation, at a concentration of 100 or 150 µg/ml. An indirect immunofluorescence assay demonstrated that C8 may inhibit p65/NF‑κB nuclear translocation. Additionally, C8 prevented an increase in cytokine mRNA expression, including interleukin (IL)‑1β, IL‑6, IL‑8 and C‑C motif chemokine 2 (MCP‑1). Furthermore, the Bio‑Plex assay results indicated that the protein expression of IL‑6, IL‑8, TNF‑α, C‑X‑C motif chemokine 10, MCP‑1 and C‑C motif chemokine 5 was inhibited. These findings suggest that C8 has the potential to be developed into an anti‑inflammatory drug for the prevention and treatment of influenza A virus infection.

Antiinflammatory phytochemicals against virus‐induced hyperinflammatory responses: Scope, rationale, application, and limitations

“…Others have demonstrated that a pterodontic acid-rich composition from L. pterodonta is effective against a broad spectrum of influenza viruses, including human and avian influenza virus infection (Wang et al, 2018). This mode of action was associated with inhibition of…”

“…Besides this, the study showed the in vitro antiviral activity of pterodontic acid by inhibition of influenza A virus replication via blocking the nuclear export of viral ribonucleoprotein complexes. Others have demonstrated that a pterodontic acid‐rich composition from L. pterodonta is effective against a broad spectrum of influenza viruses, including human and avian influenza virus infection (Wang et al, 2018). This mode of action was associated with inhibition of TLR7, MyD88, TNF receptor‐associated factor, in addition to dampening the p65 phosphorylation in A549 human alveolar basal epithelial cells.…”

Novel Fatty Acid in Cordyceps Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways

“…Protein concentration was measured using a bicinchoninic acid protein assay kit (Invitrogen Life Technologies). Western blots were performed on PVDF membranes as described, using primary antibodies (CST Biological Reagents) to identify TLR-3, RIG-I, IRF-3, p -IRF-3, p 65, p - p 65, ERK, p -ERK, Akt, p -Akt, p 38, p - p 38, STAT2, p -STAT2, and GAPDH at a dilution following the manufacturer’s protocol. After incubation with primary antibodies, horseradish peroxidase-conjugated secondary antibody (CST Biological Reagents) was added to PVDF membranes for 60 min at room temperature (RT).…”

Pterodontic Acid Isolated from Laggera pterodontaInhibits Dengue Virus Serotype 2 Infection

“…Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection [7]. No specific treatment exists for dengue fever, and vector control has been largely ineffective at preventing the rapid geographic spread of the disease [8][9][10]. Therefore, it is necessary to develop an innovative antiviral drug.…”